Biomedical subjects

J A Spaan

Publications and source records attributed to J A Spaan.

At least 19 recordsLinked to original sources

PubMed2001

Role of variability in microvascular resistance on fractional flow reserve and coronary blood flow velocity reserve in intermediate coronary lesions.

BACKGROUND: Fractional flow reserve (FFR) and coronary blood flow velocity reserve (CFR) represent physiological quantities used to evaluate coronary lesion severity and to make clinical decisions. A comparison between the outcomes of both diagnostic techniques has not been performed in a large cohort of patients with intermediate coronary lesions. METHODS AND RESULTS: FFR and CFR were assessed in 126 consecutive patients with 150 intermediate coronary lesions (between 40% and 70% diameter stenosis by visual assessment). Agreement between outcomes of FFR and CFR, categorized at cut-off values of 0.75 and 2.0, respectively, was observed in 109 coronary lesions (73%), whereas discordant outcomes were present in 41 lesions (27%). In 26 of these 41 lesions, FFR was <0.75 and CFR>or=2.0 (group A); in the remaining 15 lesions, FFR was >or=0.75 and CFR<2.0 (group B). Minimum microvascular resistance, defined as the ratio of mean distal pressure to average peak blood flow velocity during maximum hyperemia, showed a large variability (overall range, 0.65 to 4.64 mm Hg x cm(-1) x s(-1)) and was significantly higher in group B than in group A (2.42+/-0.77 versus 1.91+/-0.70 mm Hg x cm(-1) x s(-1); P:=0.034). CONCLUSIONS: Our findings demonstrate the prominent role of microvascular resistance in modulating the relationship between FFR and CFR and emphasize the importance of combined pressure and flow velocity measurements to evaluate coronary lesion severity and microvascular involvement.

Angina Pectoris↗

PubMed2001

Laser pulse impact on rat mesenteric blood vessels in relation to laser treatment of port wine stain.

BACKGROUND AND OBJECTIVE: To study the impact of laser pulses on animal microvasculature as a model for laser treatment of port wine stains. STUDY DESIGN/MATERIALS AND METHODS: Rat mesenteric blood vessels were irradiated with a laser pulse (585 nm, 0.2-0.6 ms pulse duration, 0.5-30 J/cm(2) radiant exposure). Video microscopy was used to assess vessel dilation, formation of intravascular thrombi, bubble formation, and vessel rupture. Changes in reflection during a laser pulse were measured by simultaneously recording the temporal behavior of the incident and reflected signals. RESULTS: A threshold radiant exposure of approximately 3 J/cm(2) was found for changes in optical properties of blood in vivo, confirming previous in vitro results. Often, laser exposure induced a significant increase in vessel diameter, up to three times the initial diameter for venules and four times for arterioles, within 200 ms after laser exposure. Arterioles were more likely to dilate than venules. Sometimes, immediately after the pulse, round structures, interpreted as being gas bubbles, were seen within the vessel lumen. CONCLUSIONS: A variety of phenomena can occur when blood vessels of sizes comparable to those in port wine stains are irradiated with laser pulses as used in port wine stain treatment. Thrombus formation and vessel rupture have been described before from histological sections of laser-irradiated port wine stains. However, vessel dilation and formation of non-transient gas bubbles as found in this study have not been described before.

Animals↗

PubMed2001

Impact of current cryopreservation procedures on mechanical and functional properties of human aortic homografts.

We evaluated the impact f standard cryopreservation on mechanical and functional properties of human aortic homografts. From 14 human heart-valve donors, the thoracic descending aorta was obtained. Effects of cryopreservation on mechanical (elastic properties and breaking stress) and smooth muscle cell (SMC) and endothelium function were tested. Cryopreservation (cryo) did not significantly affect Young's modulus of elastin (fresh: 3.1 +/- 1.0, cryo: 2.7 +/- 0.9 x 10(5) Nm(-2)), collagen recruitment pressure (fresh: 1.1 +/- 0.3, cryo: 1.1 +/- 0.4 x 10(4) Nm(-2)), distensibility (fresh: 3.8 +/- 1.8, cryo: 3.6 +/- 1.6 x 10(5) N(-1)m2), or breaking stress (fresh: 2.4 +/- 1.0, cryo: 2.2 +/- 1.0 x 10(6) Nm(-2)). Following explantation, no endothelium-dependent relaxation was found. SMC function and endothelium-independent relaxation were mainly intact after explantation but significantly decreased after cryopreservation. Aortic mechanical properties are not influenced by cryopreservation. Following explantation, almost no endothelial cell function is present, and SMC contractility is strongly affected after cryopreservation.

Adolescent↗

PubMed2001

Role of protein kinase C in myogenic calcium-contraction coupling of rat cannulated mesenteric small arteries.

1. The present study was designed to determine the role of protein kinase C (PKC) in the myogenic response of small arteries. In particular, we tested whether inhibition of PKC reverses the previously found pressure-induced elevation of contractile element calcium sensitivity. 2. Rat mesenteric small arteries were cannulated and pressurized. The internal diameter was continuously monitored with a video camera and intracellular calcium levels were measured by means of fura-2. Myogenic responses were observed when the pressure was raised stepwise from 20 to 60 and then to 100 mmHg in physiological saline solution and during application of phenylephrine (0.1 or 1 micromol/L) or potassium (36 mmol/L). 3. The PKC inhibitors H-7 (20 micromol/L), staurosporine (100 nmol/L) and calphostin C (10 nmol/L) all completely abolished the myogenic response. Whereas staurosporine caused an ongoing reduction in intracellular calcium, pressure-induced calcium transients were not affected by either H-7 or calphostin C. In particular, the slope of the wall tension-calcium relationship remained similar in the presence of both H-7 and calphostin C, despite an upward shift of this relationship to higher calcium levels in the case of calphostin C. 4. These results show that activity of PKC isoform(s) is essential for myogenic calcium-contraction coupling.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2001

Vasomotor effects of arg-gly-asp (RGD) peptides are limited and not related to endothelium-derived hyperpolarizing factor-mediated relaxation in rat mesenteric arteries.

1. In the present study we tested the effect of arg-gly-asp (RGD) peptides on vasomotor responses in rat isolated mesenteric arteries. More specifically, the hypothesis was tested that RGD interaction with integrins mediates relaxation attributed to endothelium-derived hyperpolarizing factor (EDHF). 2. The presence of the beta3 integrin subunit was shown by western blot analysis. To study its functional role, arteries (355 +/- 11 microm; n = 50) were mounted in a wire myograph set-up to measure isometric force generation. After blockade of nitric oxide synthesis with N(G)-nitro-L-arginine (0.1 mmol/L) and prostaglandin synthesis with indomethacin (10 micromol/L), methacholine (10 micromol/L) induced a transient relaxation within 1 min of 72 +/- 4.0% (as percentage of precontraction with phenylephrine; n = 27). 3. These responses were inhibited by a 60 mmol/L potassium buffer (18 +/- 6.0%; n = 6) or endothelium denudation (12 +/- 3.2%; n = 7), consistent with EDHF. 4. A function-blocking monoclonal antibody against the integrin beta3 chain did not affect relaxation. 5. The RGD peptides gly-arg-gly-asp-thr-pro (GRGDTP), gly-arg-gly-asp-ser (GRGDS) and cyclic RGD, ligands for the RGD binding site of integrins, also did not affect relaxation induced by methacholine. 6. Cyclic RGD increased contraction from 91 +/- 3 to 98 +/- 3% (as percentage of 120 mmol/L potassium). 7. In conclusion, these data show that vasomotor responses related to integrins are small and not involved in hyperpolarization attributed to EDHF in rat mesenteric artery.

Animals↗

PubMed2001

Role of Rho-associated protein kinase in tone and calcium sensitivity of cannulated rat mesenteric small arteries.

The regulation of vascular tone includes modulation of contractile element calcium sensitivity. We tested the involvement of the Rho-associated protein kinase p160ROCK in tone and calcium sensitivity of cannulated rat mesenteric small arteries. These vessels developed basal tone and showed myogenic responses upon pressure steps, resulting from an increase in calcium in combination with a high contractile element calcium sensitivity. Y-27632, believed to be a specific p160ROCK inhibitor, caused concentration-dependent inhibition of basal tone, with near full inhibition at 3 microM. At this concentration, myogenic responses were absent and stepwise pressure elevation resulted in severe vascular distension. Y-27632 did not affect pressure-induced changes in intracellular calcium but rather reduced pressure-induced as well as phenylephrine-induced calcium sensitisation. Thus in the presence of the blocker, for a given calcium concentration, tone was greatly reduced, and the divergence in sensitivity between pressure and phenylephrine as stimuli on the one hand and potassium on the other disappeared. K+ (125 mM) and ionomycin still caused contraction in the presence of the p160ROCK blocker. These data show that in pressurised small arteries the Rho-p160ROCK pathway is active in the absence of vasoconstrictors, keeping the vessels in a state of high calcium sensitivity and basal tone.

Amides↗

PubMed2001

Biophysical properties of the normal-sized aorta in patients with Marfan syndrome: evaluation with MR flow mapping.

PURPOSE: To investigate the feasibility of magnetic resonance (MR) flow mapping in the assessment of aortic biophysical properties in patients with Marfan syndrome and to detect differences in biophysical properties in the normal-sized aorta distal to the aortic root between these patients and matched control subjects. MATERIALS AND METHODS: Seventy-eight patients with Marfan syndrome with aortic root dilatation and 23 matched control subjects underwent MR flow mapping in four locations in the normal-sized aorta (1, ascending aorta; 2, thoracic descending aorta; 3, descending aorta at the level of the diaphragm; and 4, abdominal descending aorta). Distensibility at each location and flow wave velocity between locations were calculated. RESULTS: Compared with the control subjects, patients with Marfan syndrome had decreased aortic distensibility at three of the four locations (levels 1, 2, and 4; P <.05) and increased flow wave velocity between all locations (P <.05) in the aorta. In patients with Marfan syndrome, flow wave velocity was also significantly increased along the entire aortic tract beyond the aortic root (from level 1 to level 4). CONCLUSION: MR imaging reveals abnormal biophysical properties of the normal-sized aorta in patients with Marfan syndrome. Monitoring of these properties is relevant for evaluating disease progression and treatment options.

Adolescent↗

PubMed2001

Elevated capillary tube hematocrit reflects degradation of endothelial cell glycocalyx by oxidized LDL.

Proteoglycans and plasma proteins bound to the endothelial cell glycocalyx are essential for vascular function, but at the same time, they lower capillary tube hematocrit by reducing capillary volume available to flowing blood. Because oxidized low-density lipoproteins (oxLDL) reduce the effective thickness of the glycocalyx (Vink H, Constantinescu AA, and Spaan JAE. Circulation 101: 1500-1502, 2000), we designed the present study to determine whether this is caused by pathological degradation of glycocalyx constituents or increased glycocalyx deformation by elevated shear forces of flowing blood. Capillaries from the right cremaster muscle of 24 hamsters were examined by using intravital microscopy after systemic administration of normal LDL (n = 4), moderate oxLDL (6-h oxidation with CuSO(4), n = 7), severe oxLDL (18-h oxidation, n = 5), and moderate oxLDL plus superoxide dismutase (SOD) and catalase (n = 8). Capillary tube hematocrit increased from 0.16 +/- 0.03 to 0.37 +/- 0.05 and from 0.15 +/- 0.01 to 0.31 +/- 0.03 after moderate oxLDL and severe oxLDL, respectively. These changes were paralleled by increases in red blood cell flux from 8.7 +/- 1.9 to 13.8 +/- 3 and from 10.7 +/- 2.1 to 16.3 +/- 3.2 cells/s after moderate oxLDL and severe oxLDL, respectively, in the absence of changes in anatomic capillary diameter. Red blood cell velocity, as a measure for the shear forces on the glycocalyx, was not affected by oxLDL, whereas tissue pretreatment with SOD and catalase completely abolished the effects of oxLDL on glycocalyx thickness, capillary hematocrit, and red blood cell flux. We conclude that elevation of capillary tube hematocrit by oxLDL reflects degradation of the endothelial glycocalyx by oxygen-derived free radicals.

Animals↗

PubMed2001

Stenosis differentially affects subendocardial and subepicardial arterioles in vivo.

The presence of a coronary stenosis results primarily in subendocardial ischemia. Apart from the decrease in coronary perfusion pressure, a stenosis also decreases coronary flow pulsations. Applying a coronary perfusion system, we compared the autoregulatory response of subendocardial (n = 10) and subepicardial (n = 12) arterioles (<120 microm) after stepwise decreases in coronary arterial pressure from 100 to 70, 50, and 30 mmHg in vivo in dogs (n = 9). Pressure steps were performed with and without stenosis on the perfusion line. Maximal arteriolar diameter during the cardiac cycle was determined and normalized to its value at 100 mmHg. The initial decrease in diameter during reductions in pressure was significantly larger at the subendocardium. Diameters of subendocardial and subepicardial arterioles were similar 10--15 s after the decrease in pressure without stenosis. However, stenosis decreased the dilatory response of the subendocardial arterioles significantly. This decreased dilatory response was also evidenced by a lower coronary inflow at similar average pressure in the presence of a stenosis. Inhibition of nitric oxide production with N(G)-monomethyl-L-arginine abrogated the effect of the stenosis on flow. We conclude that the decrease in pressure caused by a stenosis in vivo results in a larger decrease in diameter of the subendocardial arterioles than in the subepicardial arterioles, and furthermore stenosis selectively decreases the dilatory response of subendocardial arterioles. These two findings expand our understanding of subendocardial vulnerability to ischemia.

Animals↗

PubMed2001

Evidence for stretch-induced resistance increase of proximal coronary microcirculation.

We investigated the influence of stretch on regional hemodynamic parameters of the septal circulation. We used a similar experimental setup and mathematical model, as described previously (14). Five ventricular septa were isolated from anesthetized dogs, sutured to a biaxial stretching apparatus, and perfused with an oxygenated perfluorochemical emulsion at maximal vasodilation. Under unloaded and biaxially stretched conditions, flow and septal thickness (to index vascular volume) were measured continuously. Pressure was varied sinusoidally at 30, 50, and 70 mmHg with amplitude of 7.5 mmHg over frequencies ranging between 0.015 and 7 Hz. Admittance (flow/pressure) and capacitance (thickness/pressure) transfer functions were calculated and interpreted in terms of a two-compartmental model with volume-dependent resistances. Parameter estimation showed that the proximal resistance and compliance were unaffected, whereas the resistance of the proximal part of the microcirculation, including the small arterioles, increased with stretch. The effect of stretch on the distal resistance and capacitance, however, could not be determined unequivocally.

Animals↗

PubMed2000

Oxidized lipoproteins degrade the endothelial surface layer : implications for platelet-endothelial cell adhesion.

BACKGROUND: Flowing erythrocytes and platelets are separated from the luminal endothelial cell (EC) surface by a 0.5-microm-wide space named the endothelial surface layer. We hypothesized that the disruption of the endothelial surface layer by oxidized low-density lipoproteins (Ox-LDL) contributes to atherogenic increases in vascular wall adhesiveness. METHODS AND RESULTS: The hamster cremaster muscle preparation was used for intravital microscopic observation of the distance between erythrocytes and the capillary EC surface. Moderate Ox-LDL was prepared by exposing native LDL to CuSO(4) for 6 hours. The dimension of the EC surface layer averaged 0.6+/-0.1 microm during control situations, but a bolus intravenous injection of Ox-LDL (0.4 mg/100 g of body weight) transiently diminished the EC surface layer by 60% within 25 minutes, which correlated with a transient increase in the number of platelet-EC adhesions. Combined administration of superoxide dismutase and catalase completely blocked the effect of Ox-LDL on the dimension of the EC surface layer and inhibited platelet-EC adhesion. CONCLUSIONS: Oxygen-derived free radicals mediate the disruption of the EC surface layer and increase vascular wall adhesiveness by Ox-LDL.

Animals↗

PubMed2000

Metabolic coronary-flow regulation and exogenous nitric oxide in human coronary artery disease: assessment by intravenous administration of nitroglycerin.

We sought to evaluate the effect of intravenous administration of the nitric oxide--donor substance nitroglycerin (NTG) on metabolic coronary-flow regulation in patients with coronary artery disease (CAD). In 12 patients with stable CAD, we measured coronary sinus blood flow and myocardial oxygen supply and consumption (MVO2) at sinus rhythm and during atrial pacing (30 beats/min above sinus rate), both at control and during infusion of NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min. To study metabolic coronary vasodilation, changes in myocardial oxygen supply were related to pacing-induced changes in MVO2, by using standard regression analysis. The myocardial oxygen supply/consumption ratio (i.e., the slope of the regression line at control, characterizing physiological metabolic coronary flow regulation) was compared with the ratios obtained during infusion of NTG. Compared with control measurements, NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min, attenuated pacing-induced increases in MVO2 by 29 and 60%, respectively, whereas coronary blood flow during pacing remained unchanged. At control, normal metabolic coronary-flow regulation resulted in a myocardial oxygen supply/demand ratio of 1.39 (95% CI, 1.29-1.49). This ratio did not change during NTG, 1 microg/kg/min: 1.44 (95% CI, 1.33-1.56). However, during NTG, 2 microg/kg/min, this ratio significantly increased to 1.84 (95% CI, 1.63-2.05; p<0.01). Intravenous administration of high-dose NTG, a donor of exogenous NO, blunts pacing-induced increases in MVO2 and may increase metabolic coronary vasodilation in patients with CAD.

Aged↗

PubMed2000

Dynamics of flow, resistance, and intramural vascular volume in canine coronary circulation.

Varying coronary volume will vary vascular resistance and thereby have an effect on coronary hemodynamics. Six ventricular septa were isolated from anesthetized dogs, dispersed in a biaxial stretch apparatus at diastolic stress, and perfused artificially with an oxygenated perfluorochemical emulsion at maximal vasodilation. Flow and thickness were measured continuously by an electromagnetic flow probe and sonomicrometer. Pressure was varied sinusoidally around 30, 50, and 70 mmHg with an amplitude of 7.5 mmHg; frequencies ranged between 0.015 and 7 Hz. Bode plots of admittance (flow/pressure) and capacitance (scaled thickness/pressure) were constructed. A two-compartment model was used in which the resistances vary with volume. Realistic values of microvascular compliance ( approximately 0.3 ml x mmHg(-1) x 100 g(-1)) were found. Values 10 times higher were then found when resistances were forced to be constant. We concluded that volume dependence of resistances have to be taken into account when dynamic or static pressure-flow relations are studied and conceal the effect of a large intramyocardial compliance on arterial hemodynamics.

Animals↗

PubMed2000

Organoid culture of cannulated rat resistance arteries: effect of serum factors on vasoactivity and remodeling.

We developed an organoid culture technique to study the mechanisms involved in arterial remodeling. Resistance arteries were isolated from rat cremaster muscle and mounted in a pressure myograph at 75 mmHg. Vessels were studied during a 4-day culture period in DMEM with either 2% albumin, 10% heat-inactivated FCS (HI-FCS) or 10% dialyzed HI-FCS (12 kDa cut off) added to the perfusate. The albumin group showed a gradual loss of endothelial function and integrity, whereas smooth muscle agonist and myogenic responses were retained. No remodeling was observed. Vessels cultured in the presence of serum showed a progressive constriction. Smooth muscle responses and substance P-induced endothelium-dependent dilation were maintained. An inward remodeling of 17 +/- 4% in the HI-FCS group and 26 +/- 3% in the dialyzed HI-FCS group was found, while media cross-sectional areas were unchanged. These data show that pressurized resistance arteries can be maintained in culture for several days and undergo eutrophic remodeling in vitro in the presence of high molecular weight serum factors.

Acetylcholine↗

PubMed2000

Myogenic reactivity and resistance distribution in the coronary arterial tree: a model study.

The objectives of this study were to evaluate the myogenic behavior of blood vessels and their interaction within the coronary arterial tree and to evaluate the possible role of the myogenic response in autoregulation. The model consists of 10 compartments in series, each representing a class of vessel sizes. Diameter and resistance in each class are determined by their value at full dilation (d(p,) R(p)) and by the myogenic response. Three distributions of R(p) and three distributions of myogenic strength, M(i) (slope of pressure-diameter curve, range -0.05 to -0.4%/mmHg) were evaluated (9 cases). It was found that larger vessels attenuate the myogenic activity of smaller vessels and that myogenic responsiveness is sufficient to achieve autoregulation. When M(i) has a maximum in vessels of 84 microm, the maximum effect of perfusion pressure on active diameter occurs in vessels between 123 and 181 microm, depending on the distribution of R(p). Distribution of resistance and control mechanisms in the coronary arterial tree are important for interpretation of individual vessel responses as observed in vivo.

Algorithms↗

PubMed1999

The influence of aging and aortic stiffness on permanent dilation and breaking stress of the thoracic descending aorta.

OBJECTIVE: To assess the influence of aging and aortic stiffness on the extent of irreversible deformation and breaking stress of the human thoracic aorta. METHODS: From 14 human heart valve donors without aortic disease (mean age 35 years, range 8-59 years), 14 intact segments of the thoracic descending aorta were studied within 48 h after cardiac arrest. In an experimental setup, the segments were submitted to increasing hydrostatic pressure loads, both statically and dynamically, while radius and wall thickness were monitored echocardiographically. Pressure-radius curves were constructed. Radius and wall thickness were determined at a pressure of 100 mmHg. Radius at elastin resting length and collagen recruitment pressure (Pcol, mmHg) were derived from the pressure-radius relationship and stress-strain curves were constructed to yield Young's moduli of elastin and collagen. Distensibility (D, mmHg-1) was determined while loading the segment with a sinusoidal pressure wave of 120/50 mmHg at both 0.5 and 1 Hz. Subsequently increasing static pressure loads of 400, 800, 1200 and 1600 mmHg were applied. After each pressure load, the increase in aortic radius at a pressure of 100 mmHg (Rinc) was determined. The experiment continued until rupture occurred and breaking stress (sigma break, N m-2) was calculated, donor age and aortic stiffness were correlated with Rinc and sigma break of the aortic segments. RESULTS: Mean breaking stress of the 14 segments was 2.7 x 10(6) N m-2. Breaking stress was negatively correlated with age (r2 = 0.66) and positively with D (r2 = 0.44) and with Pcol (r2 = 0.18). Seven segments survived a pressure load of 800 mmHg, in these vessels, the extent of irreversible dilation was positively correlated with age (r2 = 0.42) and negatively with D (r2 = 0.40) and Pcol (r2 = 0.40). CONCLUSION: Permanent deformation and rupture of the human thoracic aorta following pressure overload are influenced by age, distensibility and collagen recruitment pressure.

Adolescent↗

PubMed1999

Prolonged diastolic time fraction protects myocardial perfusion when coronary blood flow is reduced.

BACKGROUND: Because coronary blood flow is impeded during systole, the duration of diastole is an important determinant of myocardial perfusion. The aim of this study was to show that coronary flow modulates the duration of diastole at constant heart rate. METHODS AND RESULTS: In anesthetized, open-chest dogs, diastolic time fraction (DTF) increased significantly when coronary flow was reduced by lowering perfusion pressure from 100 to 70, 55, and 40 mm Hg. On average, DTF increased from 0.47+/-0.04 to 0.55+/-0.03 after a pressure step from 100 to 40 mm Hg in control, from 0.42+/-0.04 to 0.47+/-0.04 after administration of adenosine, and from 0.46+/-0.07 to 0.55+/-0.06 after L-NMMA (mean+/-SD, 6 dogs for control and adenosine, 4 dogs for L-NMMA, all P<0.05). Flow normalized to its value at full dilation and pressure of 90 mm Hg (375+/-25 mL/min) increased during the period of reduced pressure at 40 mm Hg; control, from 0.005+/-63 (2 seconds after pressure step) to 0.09+/-0.06 (15 seconds after pressure step); with adenosine, from 0.19+/-0.06 to 0. 22+/-0.06; and with L-NMMA, from 0.013+/-0.007 to 0.12+/-0.02 (all P<0.05). The increase in DTF at low pressure may be explained by a decrease in interstitial volume at low pressure, which either decreases the preload of the myocytes or reduces the buffer capacity for ions determining repolarization, thereby causing an earlier onset of relaxation. CONCLUSIONS: Because the largest increase in DTF occurs at pressures below the autoregulatory range when blood flow to the subendocardium is closely related to DTF, modulation of DTF by coronary blood flow can provide an important regulatory mechanism to match supply and demand of the myocardium when vasodilatory reserve is exhausted.

Adenosine↗

PubMed1999

Interaction between Gregg's phenomenon and coronary flow control: a model study.

Coronary perfusion pressure, Pp, affects coronary arterial resistance, Ra, (autoregulation) as well as myocardial oxygen consumption, MVO2 (Gregg's phenomenon). The interaction between the effects of Pp and MVO2 on coronary flow control was investigated using a coronary flow control model. Model analysis predicts that response of the pressure-flow ratio, p/q(t), following a change in Pp depends on the sensitivity of Ra to a change in tissue oxygen concentration (tone sensitivity) and on the sensitivity of MVO2 to a change in capillary pressure (Gregg's sensitivity). At high tone sensitivity Gregg's effect is small, whereas at high Gregg's sensitivity autoregulation is attenuated. In experiments glibenclamide decelerated the p/q(t) in response to a pressure step by a factor of four. However, the proposed model demonstrates that this is compatible with a reduction in rate of change of Ra by a factor of ten. This is due to the interaction of negative and positive feedback gains in the model. Model analysis demonstrates that autoregulation and Gregg's phenomenon compete with each other in controlling coronary flow.

Animals↗