Alterations In Perfusion Pressure Research Articles

Effects of Mechanical Dyssynchrony on Coronary Flow: Insights From a Computational Model of Coupled Coronary Perfusion With Systemic Circulation.

Mechanical dyssynchrony affects left ventricular (LV) mechanics and coronary perfusion. Due to the confounding effects of their bi-directional interactions, the mechanisms behind these changes are difficult to isolate from experimental and clinical studies alone. Here, we develop and calibrate a closed-loop computational model that couples the systemic circulation, LV mechanics, and coronary perfusion. The model is applied to simulate the impact of mechanical dyssynchrony on coronary flow in the left anterior descending artery (LAD) and left circumflex artery (LCX) territories caused by regional alterations in perfusion pressure and intramyocardial pressure (IMP). We also investigate the effects of regional coronary flow alterations on regional LV contractility in mechanical dyssynchrony based on prescribed contractility-flow relationships without considering autoregulation. The model predicts that LCX and LAD flows are reduced by 7.2%, and increased by 17.1%, respectively, in mechanical dyssynchrony with a systolic dyssynchrony index of 10% when the LAD's IMP is synchronous with the arterial pressure. The LAD flow is reduced by 11.6% only when its IMP is delayed with respect to the arterial pressure by 0.07 s. When contractility is sensitive to coronary flow, mechanical dyssynchrony can affect global LV mechanics, IMPs and contractility that in turn, further affect the coronary flow in a feedback loop that results in a substantial reduction of dPLV/dt, indicative of ischemia. Taken together, these findings imply that regional IMPs play a significant role in affecting regional coronary flows in mechanical dyssynchrony and the changes in regional coronary flow may produce ischemia when contractility is sensitive to the changes in coronary flow.

Disentangling the Gordian knot of local metabolic control of coronary blood flow.

Recognition that coronary blood flow is tightly coupled with myocardial metabolism has been appreciated for well over half a century. However, exactly how coronary microvascular resistance is tightly coupled with myocardial oxygen consumption (MV̇o2) remains one of the most highly contested mysteries of the coronary circulation to this day. Understanding the mechanisms responsible for local metabolic control of coronary blood flow has been confounded by continued debate regarding both anticipated experimental outcomes and data interpretation. For a number of years, coronary venous Po2 has been generally accepted as a measure of myocardial tissue oxygenation and thus the classically proposed error signal for the generation of vasodilator metabolites in the heart. However, interpretation of changes in coronary venous Po2 relative to MV̇o2 are quite nuanced, inherently circular in nature, and subject to confounding influences that remain largely unaccounted for. The purpose of this review is to highlight difficulties in interpreting the complex interrelationship between key coronary outcome variables and the arguments that emerge from prior studies performed during exercise, hemodilution, hypoxemia, and alterations in perfusion pressure. Furthermore, potential paths forward are proposed to help to facilitate further dialogue and study to ultimately unravel what has become the Gordian knot of the coronary circulation.

Two-Dimensional Time-Harmonic Elastography of the Human Liver and Spleen

Measurement of shear wave speed of the liver and spleen by elastography is an established diagnostic procedure for the detection of hepatic fibrosis, portal hypertension and esophageal varices. However, current elastography systems are limited by the size and penetration depth of elastographic windows. In this study, 2D time-harmonic elastography is proposed for generating full field-of-view shear wave speed maps in great depth. Two-dimensional time-harmonic elastography uses external harmonic stimulation at multiple frequencies to create compound shear wave speed maps. The method is tested in a phantom with soft and stiff inclusions and used for elastography of the liver and spleen in 13 asymptomatic volunteers. Each volunteer was scanned twice to determine the sensitivity of the method to physiologic variations: first, after 2 h of fasting, and a second time, 15 min after drinking 1 L of water. The wave speed maps of the phantom clearly identified the soft and stiff inclusions, yielding values that were consistent with those from magnetic resonance elastography. In vivo wave speed values were 1.49 ± 0.11 m/s for the liver and 2.03 ± 0.15 m/s for the spleen in a lower-frequency band centered at 40 Hz and 3.15 ± 0.30 m/s for the spleen in a higher-frequency band centered at 120 Hz. After water intake, wave speed values increased by 6% in the liver (p = 0.002) and decreased in the spleen by 4% (p = 0.021, low-frequency band) and 6% (p = 0.0002, high-frequency band), suggesting the high sensitivity of the method to altered blood flow and perfusion pressure. Two-dimensional time-harmonic elastography of the liver and spleen is a promising method for measuring tissue stiffness at different states of blood flow and perfusion in a large tissue window and at great penetration depth.

Pressure natriuresis and the renal control of arterial blood pressure.

The regulation of extracellular fluid volume by renal sodium excretion lies at the centre of blood pressure homeostasis. Renal perfusion pressure can directly regulate sodium reabsorption in the proximal tubule. This acute pressure natriuresis response is a uniquely powerful means of stabilizing long-term blood pressure around a set point. By logical extension, deviation from the set point can only be sustained if the pressure natriuresis mechanism is impaired, suggesting that hypertension is caused or sustained by a defect in the relationship between renal perfusion pressure and sodium excretion. Here we describe the role of pressure natriuresis in blood pressure control and outline the cascade of biophysical and paracrine events in the renal medulla that integrate the vascular and tubular response to altered perfusion pressure. Pressure natriuresis is impaired in hypertension and mechanistic insight into dysfunction comes from genetic analysis of blood pressure disorders. Transplantation studies in rats show that blood pressure is determined by the genotype of the kidney and Mendelian hypertension indicates that the distal nephron influences the overall natriuretic efficiency. These approaches and the outcomes of genome-wide-association studies broaden our view of blood pressure control, suggesting that renal sympathetic nerve activity and local inflammation can impair pressure natriuresis to cause hypertension. Understanding how these systems interact is necessary to tackle the global burden of hypertension.

The Meniere attack: An ischemia/reperfusion disorder of inner ear sensory tissues

We believe Meniere attacks arise as a chance association of endolymphatic hydrops and vascular risk factors for intracerebral ischemia. Hydrops acts as a variable Starling resistor upon the inner ear vasculature that is capable of inducing ischemic attacks only in people with reduced perfusion pressure in the ear. The unique characteristics of the attacks (loss of vestibular response and hearing acutely followed by a return to apparent normalcy over hours) are explained by the differential sensitivity of the inner ear tissues to transient ischemia, with the sensory tissues (dendrites, hair cells) vulnerable to hours-long ischemia/reperfusion injury, and the stria vulnerable to ischemia due to its high metabolic rate. Permanent hearing loss and vestibular damage after many attacks would result when small areas of irreversible sensory cell damage accumulate and become confluent.This theory is supported by the strong correlation of hydrops with Meniere attacks, the finding that autoregulation of cochlear blood flow is impaired in the hydropic ear, and studies demonstrating that symptoms and signs in people and in animal models vary with conditions that alter perfusion pressure in the inner ear. Induction of Meniere attacks in animal models requires both hydrops and a mechanism that reduces perfusion pressure, such as epinephrine injection or head dependency. There is a strong clinical association between Meniere attacks and disorders that increase the risk for cerebrovascular ischemia, such as migraine. The excitable tissues in the sensory structures have long been known to be more vulnerable to ischemia than the remaining aural tissues, and are now known to be vulnerable to excitotoxicity induced by ischemia/reperfusion. This correlates well with autopsy evidence of damage to dendrites and hair cells and with strial atrophy in late Meniere disease cases.If this hypothesis is confirmed, treatment of vascular risk factors may allow control of symptoms and result in a decreased need for ablative procedures in this disorder. If attacks are controlled, the previously inevitable progression to severe hearing loss may be preventable in some cases.

Genetic interference with peroxisome proliferator‐activated receptor γ (PPARγ) in smooth muscle enhances cerebrovascular myogenic tone via a rho kinase‐dependent mechanism

Cerebral arteries are important resistance vessels and play a crucial role in regulating cerebral blood flow (CBF). Myogenic responses are a key element of mechanisms that regulate CBF during altered perfusion pressure. PPARγ may play a protective role in the vasculature by inhibiting increases in vascular tone. We tested whether cell‐specific interference with PPARγ in smooth muscle would increase myogenic tone in cerebral arteries. We studied mice expressing a dominant negative mutation of human PPARγ in smooth muscle (TG) and littermate controls (NT). Under baseline conditions (75 mmHg), middle cerebral arteries (MCA) from TG mice generated more myogenic tone compared with arteries from NT (31±4% vs. 9±2% of max diameter n=7–8). Myogenic reactivity was augmented in MCA from TG mice over a range of pressures (15–150 mmHg) compared with NT whereas diameter in Ca2+ free conditions was similar between groups. Treatment of MCA from TG mice with the rho kinase inhibitor Y27632 abolished the augmentation of myogenic tone (34±5% vs. 9±4% of max diameter n=7). Treatment of vessels from TG with the superoxide dismutase mimetic tempol reduced myogenic tone by ~30% (33±4% vs. 21±2% of max diameter n=6). These findings suggest that PPARγ in vascular muscle regulates rho kinase, influencing myogenic tone in small resistance arteries. This work was supported by NIH grants NS24621 and HL62984 and AHA Fellowship 12POST9150027.

Neurologically generated electric currents of myocytes are the most rapid stimulus for the capillary pumps, even preceding muscle contraction

to the editor: We appreciate Drs. Villar and Hughson's ([5][1]) excellent experiments and their scientific approach and diligence in trying to explain exercise phenomena in the circulatory system with the two widely accepted theories: for the local blood flow regulation and for the venous return. We

Effect of altered arterial perfusion pressure on vascular conductance and muscle blood flow dynamic response during exercise in humans

Changes in vascular conductance (VC) are required to counter changes in muscle perfusion pressure (MPP) to maintain muscle blood flow (MBF) during exercise. We investigated the recruitment of VC as a function of peak VC measured in three body positions at two different work rates to test the hypothesis that adaptations in VC compensated changes in MPP at low-power output (LPO), but not at high-power output (HPO). Eleven healthy volunteers exercised at LPO and HPO (repeated plantar flexion contractions at 20-30% maximal voluntary contraction, respectively) in horizontal (HOR), 35° head-down tilt (HDT), and 45° head-up tilt (HUT). Muscle blood flow velocity and popliteal diameter were measured by ultrasound to determine MBF, and VC was estimated by dividing MBF flow by MPP. Peak VC was unaffected by body position. The rates of increase in MBF and VC were significantly faster in HUT and slower in HDT than HOR, and rates were faster in LPO than HPO. During LPO exercise, the increase in, and steady-state values of, MBF were less for HUT and HDT than HOR; the increase in VC was less in HUT than HOR and HDT. During HPO exercise, MBF in the HDT was reduced compared with HOR and HUT, even though VC reached 92% VC peak, which was greater than HOR, which was, in turn, greater than HUT. Reduced MBF during HPO HDT exercise had the functional consequence of a significant increase in muscle electromyographic index, revealing the effects of MPP on O2 delivery during exercise.

Perfusion pressure and movement-induced hyperemia: evidence of limited vascular function and vasodilatory reserve with age

To better understand the mechanisms contributing to reduced blood flow with age, this study sought to elucidate the impact of altered femoral perfusion pressure (FPP) on movement-induced hyperemia. Passive leg movement was performed in 10 young (22 ± 1 yr) and 12 old (72 ± 2 yr) healthy men for 2 min, with and without a posture-induced change in FPP (~7 ± 1 ΔmmHg). Second-by-second measurements of central and peripheral hemodynamic responses were acquired noninvasively (finger photoplethysmography and Doppler ultrasound, respectively), with FPP confirmed in a subset of four young and four old subjects with arterial and venous catheters. Central hemodynamic responses (heart rate, stroke volume, cardiac output, mean arterial pressure) were not affected by age or position. The young exhibited a ~70% greater movement-induced peak change in leg blood flow (ΔLBF(peak)) in the upright-seated posture (supine: 596±68 ml/min; upright: 1,026 ± 85 ml/min). However, in the old the posture change did not alter ΔLBF(peak) (supine: 417±42 ml/min; upright: 412±56 ml/min), despite the similar increases in FPP. Similarly, movement-induced peak change in leg vascular conductance was ~80% greater for the young in the upright-seated posture (supine: 7.1 ± 0.8 ml·min(-1)·mmHg(-1); upright: 12.8 ± 1.3 ml·min(-1)·mmHg(-1)), while the old again exhibited no difference between postures (supine: 4.7 ± 0.4 ml·min(-1)·mmHg(-1); upright: 4.8 ± 0.5 ml·min(-1)·mmHg(-1)). Thus this study reveals that, unlike the young, increased FPP does not elicit an increase in movement-induced hyperemia or vasodilation in the old. In light of recent evidence that the majority of the first minute of passive movement-induced hyperemia is predominantly nitric oxide (NO) dependent in the young, these findings in the elderly may be largely due to decreased NO bioavailability, but this remains to be definitively determined.

Contractile effects of adenosine, coronary flow and perfusion pressure in murine myocardium

There is mixed evidence adenosine receptors (ARs) may enhance myocardial contractility, although this remains contentious. We assessed inotropic actions of adenosine (50 muM) and selective AR activation with 100 nM N (6)-cyclohexyladenosine (CHA; A(1)AR agonist), 25 nM 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS-21680; A(2A)AR agonist) and 100 nM 2-chloro-N (6)-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA; A(3)AR agonist) in mouse hearts perfused at constant pressure, constant flow, or conditions of stable flow and pressure (following maximal nitroprusside-mediated dilatation at constant flow). Adenosine and CGS-21680 significantly (although modestly) increased force in constant-pressure perfused hearts (</=10 mmHg elevations in systolic pressure), effects paralleled by coronary vasodilatation (</=10 ml min(-1) g(-1) elevations in flow). Neither CHA nor Cl-IB-MECA altered force or flow. With constant-flow perfusion, adenosine and CGS-21680 reduced systolic pressure in parallel with perfusion pressure. When changes in coronary flow and pressure were prevented, CGS-21680 failed to alter contractility. However, adenosine still enhanced systolic pressure up to 10 mmHg. Relations between flow, perfusion pressure and ventricular force evidence substantial Gregg effects in murine myocardium: systolic force increases transiently by approximately 1 mmHg ml(-1) min(-1) g(-1) rise in flow during the first minutes of hyperaemia and in a sustained manner (by approximately 1 mmHg mmHg(-1)) during altered perfusion pressure. These effects contribute to inotropism with AR agonism when flow/pressure is uncontrolled. In summary, we find no evidence of direct A(1) or A(3)AR-mediated inotropic responses in intact myocardium. Inotropic actions of A(2A)AR agonism appear entirely Gregg-related. Nonetheless, the endogenous agonist adenosine exerts a modest inotropic action independently of flow and perfusion pressure. The basis of this response remains to be identified.

Contractile effects of adenosine, coronary flow and perfusion pressure in murine myocardium

There is mixed evidence adenosine receptors (ARs) may enhance myocardial contractility, although this remains contentious. We assessed inotropic actions of adenosine (50 μM) and selective AR activation with 100 nM N 6-cyclohexyladenosine (CHA; A1AR agonist), 25 nM 2-[p-(2-carboxyethyl) phenethylamino]-5′-N-ethylcarboxamidoadenosine (CGS-21680; A2AAR agonist) and 100 nM 2-chloro-N 6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IB-MECA; A3AR agonist) in mouse hearts perfused at constant pressure, constant flow, or conditions of stable flow and pressure (following maximal nitroprusside-mediated dilatation at constant flow). Adenosine and CGS-21680 significantly (although modestly) increased force in constant-pressure perfused hearts (≤10 mmHg elevations in systolic pressure), effects paralleled by coronary vasodilatation (≤10 ml min−1 g−1 elevations in flow). Neither CHA nor Cl-IB-MECA altered force or flow. With constant-flow perfusion, adenosine and CGS-21680 reduced systolic pressure in parallel with perfusion pressure. When changes in coronary flow and pressure were prevented, CGS-21680 failed to alter contractility. However, adenosine still enhanced systolic pressure up to 10 mmHg. Relations between flow, perfusion pressure and ventricular force evidence substantial Gregg effects in murine myocardium: systolic force increases transiently by approximately 1 mmHg ml−1 min−1 g−1 rise in flow during the first minutes of hyperaemia and in a sustained manner (by ∼1 mmHg mmHg−1) during altered perfusion pressure. These effects contribute to inotropism with AR agonism when flow/pressure is uncontrolled. In summary, we find no evidence of direct A1 or A3AR-mediated inotropic responses in intact myocardium. Inotropic actions of A2AAR agonism appear entirely Gregg-related. Nonetheless, the endogenous agonist adenosine exerts a modest inotropic action independently of flow and perfusion pressure. The basis of this response remains to be identified.

Rhythmicity in arterial smooth muscle.

Many arteries and arterioles exhibit rhythmical contractions which are synchronous over considerable distances. This vasomotion is likely to assist in tissue perfusion especially during periods of altered metabolism or perfusion pressure. While the mechanism underlying vascular rhythmicity has been investigated for many years, it has only been recently, with the advent of imaging techniques for visualizing intracellular calcium release, that significant advances have been made. These methods, when combined with mechanical and electrophysiological recordings, have demonstrated that the rhythm depends critically on calcium released from intracellular stores within the smooth muscle cells and on cell coupling via gap junctions to synchronize oscillations in calcium release amongst adjacent cells. While these factors are common to all vessels studied to date, the contribution of voltage-dependent channels and the endothelium varies amongst different vessels. The basic mechanism for rhythmical activity in arteries thus differs from its counterpart in non-vascular smooth muscle, where specific networks of pacemaker cells generate electrical potentials which drive activity within the otherwise quiescent muscle cells.

Functional Analysis of Natriuretic Peptide Receptors in the Bladder of the Toad, Bufo marinus

This study aimed to localize and characterize natriuretic peptide binding sites in the urinary bladder of Bufo marinus and to then examine the effect of natriuretic peptides on the bladder vascular tone and water reabsorption in isolated perfused bladder preparations. Specific 125I-rat atrial natriuretic peptide (125I-rANP) binding sites were present on blood vessels, muscle, and epithelium. In tissue sections and/or isolated membranes, the binding was completely displaced by frog ANP, rat ANP, and porcine C-type natriuretic peptide (CNP; membranes only). However, a reduction in binding was observed after incubation with 125I-rANP and 1 μM of the natriuretic peptide receptor-C (NPR-C) ligand C-ANF, but residual binding remained suggesting the presence of two distinct binding sites. Electrophoresis of bladder membranes cross-linked to 125I-rANP identified two bands at approximately 70 and 140 kDa that correspond to the monomeric mass of NPR-C and the guanylate cyclase receptors, respectively. Furthermore, the presence of natriuretic peptide receptor-A and NPR-C mRNA in the bladder was demonstrated with reverse transcription–polymerase chain reaction. In addition, rat ANP, frog ANP, and porcine CNP stimulated a significant increase in cGMP generation in bladder membrane preparations, which indicated the presence of guanylate cyclase-linked receptors. In perfused bladder preparations, arginine vasotocin increased perfusion pressure and water permeability. The infusion of frog ANP or porcine CNP failed to alter perfusion pressure or water reabsorption in the presence or absence of arginine vasotocin. This study identified a well-developed natriuretic peptide receptor system in the urinary bladder of B. marinus but the function of the receptors remains unclear.

Analysis of vasoconstrictor responses to histamine in the hindlimb vascular bed of the rabbit.

Hemodynamic responses to histamine were investigated in the anesthetized rabbit. Intravenous injections of histamine induced dose-dependent decreases in systemic arterial pressure that were blocked by the H(1)-receptor antagonist pyrilamine but not the H(2) antagonist cimetidine. Injections of histamine and the H(1) agonist 6-[2-(4-imidazolyl)ethylamine]-N-(4-trifuormethylphenyl)-heptan ecardo xamide dimaleate (HTMT) into the hindlimb perfusion circuit increased hindlimb perfusion pressure, whereas the H(2) agonist dimaprit decreased perfusion pressure and the H(3)-receptor agonist R-(-)-alpha-methylhistamine did not alter perfusion pressure. Pyrilamine reduced hindlimb vasoconstrictor responses to histamine and HTMT but did not alter vasodilator responses to dimaprit. Cimetidine reduced the response to dimaprit but did not alter vasoconstrictor responses to histamine or HTMT. The H(3)-receptor antagonist thioperamide was without effect on responses to the histamine agonists. These data suggest the presence of H(1) and H(2) receptors and that histamine for the most part acts by stimulating H(1) receptors to produce vasoconstriction in the hindlimb vascular bed of the rabbit. Responses to histamine, HTMT, and norepinephrine were significantly enhanced by a nitric oxide synthase inhibitor at a time when vasodilator responses to dimaprit were unaltered and responses to acetylcholine were significantly reduced. Responses to histamine and the H(1) and H(2) agonists were not affected by the cyclooxygenase inhibitor meclofenamate or by ATP-sensitive K(+) channel, alpha-adrenergic, or angiotensin AT(1) receptor antagonists. The present data suggest that H(1) receptors mediate both systemic vasodepressor and hindlimb vasoconstrictor responses to histamine.

In vitro perfusion studies of single umbilical artery cords, the vasoactive effects of serotonin

To investigate the vascular resistance and the vasoactive effects of serotonin in arteries from single umbilical artery (SUA) cords. The preparations were sampled from 10 patients with SUA cords. The control group (n=20) was matched according to gestational age, birth weight percentile, blood pressure and proteinuria. The arterial segments were perfused in vitro employing a constant perfusion rate and measuring alterations in perfusion pressure. Following an initial test with serotonin 10(-7) M the drug was administrated in stepwise increasing concentrations from 10(-10) to 10(-5) M. The vascular resistance was significantly reduced in the SUA group compared to the control group (p<0.01). In about half of the preparations in both groups serotonin 10(-7) M induced a transient pressure decrease followed by a larger pressure increase. The remaining arteries showed a monophasic pressure increase. The maximum constrictory response calculated in percent of the prestimulatory perfusion pressure was significantly increased (p<0.01) in the SUA compared to the control group, but non-significantly increased (p=0.073) when calculated in absolute values (mmHg). Arteries in SUA cords display reduced vascular resistance compared to arteries from normal cords in in vitro perfused preparations. The response pattern to serotonin was not altered, but the constrictory response might be increased in arteries from SUA cords.

Effects of vasodilators and perfusion pressure on coronary flow and simultaneous release of nitric oxide from guinea pig isolated hearts.

The aims were to validate the use of a direct reading NO electrode, to compare the effects of diverse acting drugs on altering coronary flow (CF) and NO release, and to examine the effects of altered perfusion pressure on flow-induced changes in NO concentration [NO] in the hemoglobin free effluent of guinea pig isolated hearts. Hearts were isolated and perfused initially at a constant perfusion pressure (55 mmHg) with a modified Krebs-Ringer's solution equilibrated with 97% O2 and 3% CO2 at 37 degrees C. Heart rate, left ventricular pressure, CF, and effluent pH, pCO2, pO2, and NO generated current were monitored continuously on-line. Effluent was sampled for L-citrulline. Percent O2 extraction and O2 consumption were calculated. [NO] was quantitated with a sensitive amperometric sensor (sensitivity > or = 1 nmol/l approximately 3 pA) and a selective gas permeable membrane. The electrode was not sensitive to changes in solution pO2, flow, or pressure. The electrode was sensitive to pCO2 (-0.50 nmol/l/mmHg) and temperature (+24.5 nmol/l/degree C), so coronary effluent pCO2 was measured to compensate for a small decrease in pCO2 that occurred with an increase in coronary flow, and effluent temperature was rigidly controlled. Serotonin, bradykinin, and nitroprusside increased NO release along with CF, whereas nifedipine, butanedione monoxime, zaprinast, and bimakalim comparably increased CF but did not increase [NO] or NO release. Increases in CF (ml/g/min) and NO release (pmol/g/min), respectively, were 5.0 +/- 1 and 100 +/- 17 for 1 mumol/l serotonin, 7.5 +/- 1 and 148 +/- 18 for 100 nmol/l bradykinin, and 7.8 +/- 1 and 173 +/- 28 for 100 mumol/l nitroprusside. The increases in effluent NO by bradykinin were proportional to the increases in L-citrulline. Tetraethylammonium decreased CF, but did not change NO release, indomethacin changed neither CF nor NO release, and NG-nitro-L-arginine methyl ester (L-NAME) reduced CF by 2.6 +/- 1 ml/g/min and NO release by 25 +/- 8 pmol/g/min. An increase of CF of 8.0 +/- 0.3 ml/g/min, produced by increasing perfusion pressure from 25 to 90 mmHg, increased [NO] by 30 +/- 4 nmol/l; L-NAME but did not reduce the pressure-induced increase in CF, but reduced the increase in [NO] to 10 +/- 5 nmol/l. This study demonstrates in intact hearts real-time release of NO by several vasodilator drugs and by pressure-induced increases in flow (shear stress) and attenuation of these effects by L-NAME.

Transmural Distribution of Capillary Morphology as a Function of Coronary Perfusion Pressure in the Resting Canine Heart

Changes in coronary perfusion pressure lead to alterations in intracoronary myocardial volume that may be associated with regionally altered microvascular morphology. Transmural variations in coronary capillary geometry were quantified as a function of coronary perfusion pressure in glutaraldehyde-fixed canine hearts. Capillary volume fraction, diameter, numerical density, anisotropy, and sarcomere length were measured using computer analysis of light microscopic images of sections taken transverse or longitudinal to the muscle fiber axis. Capillary volume was 4-6% of myocardial wall volume and exhibited a significant transmural gradient, increasing from epicardium to endocardium. Vessels 4 to 5 μm in diameter with a density of 2900 mm-2 appear to increase in diameter and alter their cross-sectional shape with increasing pressure, rather than increasing in number, suggesting an effective distensibility of approximately 0.007 mm Hg-1. Quantification of vessel anisotropy was directly related to cross sectional shape and demonstrated that the capillaries are highly oriented. These findings indicate that intramyocardial capacitance is at least in part associated with nonhomogeneous changes in coronary capillary morphology with altered perfusion pressure.

Unilateral ocular vascular stress in man and retinal responsivity in the contralateral eye

Autoregulation (AR), the capacity of retinal vessels to maintain a constant flow of blood during alterations in vascular perfusion pressure, has been studied by a variety of techniques. Psychophysical and electro-physiological procedures have been used as indirect measurements of the effectiveness of AR for maintaining normal visual function during altered ocular perfusion pressure (OPP) in a single eye. However, there have been no studies in normal subjects which have investigated the responsivity of the contralateral eye while the fellow eye undergoes transient vascular stress. In the present study, the components of the bilaterally recorded scotopic flash electroretinogram (ERG) were used as objective indices of visual neural function during transiently altered OPP. The principal finding was that a decrease in the OPP for the test eye was associated with a reversible attenuation of the retinal responsivity in that eye, and a supranormal oscillatory' potential index in the contralateral eye. The existence of a central control mechanism, triggered at the eye level, may be responsible for this contralateral neural phenomenon.

Unilateral ocular vascular stress in man and retinal responsivity in the contralateral eye

Autoregulation (AR), the capacity of retinal vessels to maintain a constant flow of blood during alterations in vascular perfusion pressure, has been studied by a variety of techniques. Psychophysical and electrophysiological procedures have been used as indirect measurements of the effectiveness of AR for maintaining normal visual function during altered ocular perfusion pressure (OPP) in a single eye. However, there have been no studies in normal subjects which have investigated the responsivity of the contralateral eye while the fellow eye undergoes transient vascular stress. In the present study, the components of the bilaterally recorded scotopic flash electroretinogram (ERG) were used as objective indices of visual neural function during transiently altered OPP. The principal finding was that a decrease in the OPP for the test eye was associated with a reversible attenuation of the retinal responsivity in that eye, and a supranormal oscillatory potential index in the contralateral eye. The existence of a central control mechanism, triggered at the eye level, may be responsible for this contralateral neural phenomenon.

Continuous measurement of jugular venous oxygen saturation in response to transient elevations of blood pressure in head-injured patients

Following traumatic brain injury, continuous jugular venous oxygen saturation (SjvO2) measurements have been made and used to assess cerebral oxygenation. Transients of SjvO2 may reflect cerebral blood flow (CBF) changes if measurements are made over a short period of time during which cerebral metabolic rate for oxygen is assumed unchanged. In response to alterations in perfusion pressure, transients of SjvO2 may indicate the extent to which autoregulation has been preserved after injury. The effect of arterial pressure changes on SjvO2 was measured in 14 severely head-injured patients (Glasgow Coma Scale score < 8) within 36 hours of injury. Mean arterial blood pressure (MABP), arterial oxygen saturation, and intracranial pressure (ICP) data were also continuously recorded by a computer at the patients' bedside. The reliability of the SjvO2 oximetry measurements varied among patients, and an average 38% of SjvO2 measurements were off by more than 6% saturation, necessitating recalibration. During periods of satisfactory catheter performance, 120 instances were found in which MABP was elevated more than 8 torr (mean +/- standard deviation: 32 +/- 13 torr) due to endotracheal suctioning. In 94 of these measurements, there was an associated increase in the ICP of 5 torr or more, averaging 16.6 +/- 10.2 torr. The SjvO2 was 0.62 +/- 0.10 before the increase in MABP and rose to a peak of 0.77 +/- 0.10 during the maximum MABP elevation, suggesting increased CBF during the transient hypertension. In 34 of 37 instances of persistent blood pressure elevations lasting for more than 10 minutes (mean 16.0 +/- 8.0 minutes), the SjvO2 elevation persisted (average duration 15.0 +/- 12.4 minutes), suggesting impaired or lost autoregulatory vasoconstriction. The presence or absence of hyperemia was unrelated to the extent of the autoregulation response. Results indicate that SjvO2 rises with increasing perfusion pressure during and after endotracheal suctioning, suggesting a feeble or absent autoregulatory response following traumatic brain injury.