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Biomedical subjects

L Kuo

Publications and source records attributed to L Kuo.

69 records · Page 4Linked to original sources

Interaction of pressure- and flow-induced responses in porcine coronary resistance vessels.

Pressure-induced myogenic responses and flow-induced vasodilatory responses have been documented in coronary resistance arterioles, but the interaction of these two mechanisms and the nature of the flow-mediated response are not well understood. Experiments were designed to quantitatively study the interaction of pressure- and flow-induced responses and to characterize the nature of the substance responsible for flow-mediated dilation in isolated coronary arterioles. Subepicardial arterioles (40-80 microns) were isolated from pigs and cannulated with two glass micropipettes and then pressurized via independent reservoir systems. Flow was initiated by simultaneously moving the reservoirs in equal and opposite directions thus generating a pressure gradient (delta P) without changing the mean intraluminal pressure (IP). IP was changed by moving both reservoirs in the same direction to alter myogenic tone in the absence of flow (delta P = 0). Flow-mediated dilation competed with myogenic constriction when flow and pressure were elevated. Also, flow potentiated myogenic dilation when IP was decreased. The magnitude of flow-induced dilation was greatest at an intermediate level of vascular tone (IP = 60 cmH2O) but was attenuated at higher and lower levels of tone. In the presence of flow (delta P = 4 cmH2O), pressure-diameter relationships were shifted upward, and the magnitude of myogenic responsiveness was attenuated. Double-vessel bioassay studies indicated that a transferable substance was released from intact endothelium in response to flow. Flow-induced dilation was not affected by indomethacin but was abolished by NG-monomethyl-L-arginine or by mechanical removal of endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endothelium-dependent, flow-induced dilation of isolated coronary arterioles.

Flow-mediated dilation has been documented in large conduit coronary arteries but not in coronary arterioles. The goal of this study was to determine whether this response occurs in coronary arterioles and whether it competes with myogenic constriction. Subepicardial arterioles (40-80 microns) were isolated and cannulated with two glass micropipettes connected to independent reservoir systems. During zero flow, myogenic responses were studied over the range of intraluminal pressure (IP) between 20 and 140 cmH2O. Myogenic constrictions and dilations was observed when IP was increased (greater than 60 cmH2O) and decreased (less than 60 cmH2O), respectively. Flow was initiated by simultaneously moving the reservoirs in equal and opposite directions, thus generating a pressure gradient (delta P) without changing the mean luminal pressure (range delta P = 4-60 cmH2O). Flow-induced responses were studied at low, intermediate, and high myogenic tones by setting IP at 20, 60, and 100 cmH2O, respectively. The threshold for flow-induced dilation was delta P = 4 cmH2O, and maximum dilation was observed at delta P = 20 cmH2O. Red cell velocities in isolated arterioles at delta P of 4 and 60 cmH2O were 1.2 +/- 0.2 and 15.9 +/- 1.3 mm/s, respectively, which are within the range of those reported for coronary microvessels in vivo. The magnitude of the flow-induced dilation was greatest at the intermediate tone (60 cmH2O IP) but was attenuated at lower and higher IP. After mechanical removal of the endothelium, spontaneous tone and myogenic responses were preserved, but flow-induced dilation and bradykinin-induced dilation were abolished.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Influence of hemoconcentration on arteriolar oxygen transport in hamster striated muscle.

We investigated the influence of isovolemic hemoconcentration on microcirculatory hemodynamics and oxygen transport in the hamster cheek pouch retractor muscle. In 17 hamsters, measurements of red blood cell velocity, hematocrit, vessel diameter, segment length (L), hemoglobin oxygen saturation (SO2), and longitudinal SO2 gradient (delta SO2/L) were made in four branching orders of arterioles before and after isovolemic exchange with packed red blood cells. Hemoconcentration increased systemic hematocrit from 50 to 65%; systemic blood gases were unchanged, but mean arterial blood pressure increased approximately 10 mmHg. Accompanying this change in systemic hematocrit the microcirculatory hematocrit increased from 40 to 50%, and red blood cell velocity and computed blood flow decreased approximately 40 and 30%, respectively. In addition, delta SO2/L was significantly increased in the four arteriolar branching orders compared with control values. We estimated that approximately 10% of the oxygen that diffused across the arteriolar network was consumed by the surrounding tissue with the remainder assumed to have diffused to venules and capillaries. After hemoconcentration, the proportion of this diffusional transfer increased by approximately 80%. Convective oxygen flow remained at its control level in the first-order arterioles and progressively decreased below control in the more distal branching orders. Our analysis of arteriolar oxygen diffusion indicated that tissue oxygenation was unchanged after hemoconcentration, a result that can be attributed to a combined effect of decreased red blood cell velocity, arteriolar vasodilation, increased precapillary oxygen loss, and a relatively modest reduction in convective oxygen flow to the capillaries.

Animals↗

Coronary arteriolar myogenic response is independent of endothelium.

The purpose of this study was to investigate if myogenic responses of isolated coronary arterioles were dependent on an intact, functional endothelium. Arterioles were located in situ by intracoronary perfusion with india ink-gelatin solution and then dissected and cannulated at both ends with glass micropipettes. Intraluminal pressure was initially set at 60 cm H2O; then the pressure was altered in steps of 20 cm H2O over a range of 20-140 cm H2O. Arterioles developed spontaneous tone and exhibited a significant myogenic response in physiological saline solution (36 degrees -37 degrees C). Arteriolar dilation and constriction were observed at lower (20-60 cm H2O) and higher (60-140 cm H2O) pressures, respectively. The presence of a functional and automatically intact endothelium was confirmed by relaxation to the endothelium-dependent vasodilator bradykinin and by transmission electron microscopy, respectively. After mechanical denudation of the endothelium with a specially designed abrasive micropipette, spontaneous tone and myogenic responses were preserved. Denudation of the endothelium was verified functionally (no response to bradykinin) and with transmission electron microscopy. Moreover, the mechanical denudation technique did not deleteriously affect smooth muscle because vasoconstrictor and vasodilator responses to nonendothelial-dependent drugs were the same before and after denudation. In summary, the present study demonstrates that pressure-dependent responses occur in isolated coronary arterioles and that this response is not dependent on the endothelium. Therefore, pressure-induced changes in coronary arteriolar tone are a true myogenic response in that they originate from smooth muscle.

Acetylcholine↗

Effect of hemodilution on oxygen transport in arteriolar networks of hamster striated muscle.

Experiments were performed on the hamster cheek pouch retractor muscle to investigate the influence of isovolemic hemodilution on microcirculatory hemodynamics and the rate of oxygen transport to striated muscle. In 23 hamsters, measurements of red blood cell velocity, hematocrit, vessel diameter, segment length (L), hemoglobin oxygen saturation (SO2), and longitudinal SO2 gradient (delta SO2/L) were made in four branching orders of arterioles before and after isovolemic exchange with plasma. Hemodilution decreased systemic hematocrit from 52 to 33%. In first- through fourth-order arterioles, this degree of hemodilution resulted in an average decrease in microcirculatory hematocrit from 42 to 28% and average increases in red blood cell velocity, computed blood flow, and systemic arterial PO2 of 50, 30, and 10%, respectively. In addition, delta SO2/L was significantly smaller in second-, third-, and fourth order arterioles compared with control values. It was estimated that approximately 84% of the oxygen that diffused across the arteriolar network was transferred by diffusion to nearby venules and capillaries; the remaining oxygen was consumed by the surrounding tissue. Following hemodilution, the magnitude of diffusional transfer declined to 73%. Oxygen flow remained at its control level in the first-order arterioles and progressively increased above control with increasing branching order. The increased oxygen delivery to the capillary network after limited hemodilution can be attributed to a compensatory increase in blood flow, an increase in systemic arterial blood oxygenation, and a decrease in precapillary oxygen loss.

Algorithms↗

Myogenic activity in isolated subepicardial and subendocardial coronary arterioles.

The goal of this study was to examine myogenic responses of isolated porcine subepicardial and subendocardial arterioles (80-100 micron in diameter) within physiological ranges of intraluminal pressure. Arterioles were located by perfusion with india ink-gelatin solution then dissected and cannulated with glass micropipettes. Intraluminal pressure was altered in 20-cmH2O steps over the range of 20-140 cmH2O. IN physiological salt solution (36-37 degrees C), the coronary arterioles developed spontaneous tone and exhibited myogenic responses. At the lower pressures (20-60 cmH2O), subendocardial arterioles responded passively (diameter decreased from a control diameter at 60 cmH2O), whereas subepicardial arterioles maintained their diameters. At higher pressures (100-140 cmH2O), both subepicardial and subendocardial arterioles demonstrated myogenic constriction, but subepicardial arterioles demonstrated greater myogenic constriction than subendocardial arterioles. This implies that myogenic autoregulation in subepicardial arterioles is better than that in the subendocardial arterioles at both low and high pressures. In the presence of nitroprusside (10(-4) M), all arterioles responded to pressure changes passively, and there were no differences between subepicardial and subendocardial vessels. The functional integrity of the endothelium was verified by relaxation to substance P (10(-7) M). This is the first in vitro study to demonstrate coronary myogenic activity and transmural differences in these arteriolar responses. Our data support the concept that myogenic mechanisms in 80 to 100-micron arterioles may actively contribute to autoregulation of coronary blood flow.

Animals↗

Myogenic and flow-dependent control mechanisms in the coronary microcirculation.

We have recently gained evidence that segmental coronary microvascular diameters, and therefore resistances, are controlled by myogenic and endothelial responses to pressure and flow. Furthermore, intact heart studies are demonstrating that these mechanisms may interact importantly with the metabolic mechanisms primarily governing coronary blood flow. Further studies utilizing measurement of segmental coronary microvascular diameters in isolated microvessels and in the beating heart may elucidate the nature of these interactions. Clinical studies may determine whether reversal of endothelial impairment in the diseased coronary microcirculation contributes to autoregulatory vasodilation, increases resting myocardial perfusion, and increases the threshold for myocardial ischemia during exercise.

Animals↗

alpha-adrenergic responses of isolated canine coronary microvessels.

Although alpha-adrenergic activation is known to increase coronary microvascular resistance in vivo, the magnitude of its segmental microvascular consequences is not well understood. Quantification of these effects in vivo is hindered by escape mechanisms that minimize the influences of constrictors, and alterations in flow and pressure, which effect microvascular tone by shear stress-dependent and myogenic mechanisms, respectively. To eliminate these confounding influences, we have studied responses in vitro under conditions with these variables controlled. We evaluated the diameter changes of isolated canine coronary arterioles (110 +/- 12 microns, n = 35) response to alpha-adrenergic activation by norepinephrine (10(-10) to 10(-4) M) in the presence of beta-adrenergic blockade by alprenolol (10(-6) M). In contrast to the situation in vivo, alpha-adrenergic activation did not constrict isolated coronary arterioles, but constricted isolated coronary venules in a dose-dependent manner over a range of 10(-10) to 10(-4) M (-27 +/- 3% maximum diameter change). Coronary arteriolar alpha-adrenergic constriction was not promoted by 1) subthreshold or vasoactive doses of the vasoconstrictors KCl, angiotensin II, U46619, endothelin-1, neuropeptide Y or arginine vasopressin, 2) inhibition of the presynaptic uptake of norepinephrine by imipramine (10(-6) M), 3) inhibition of EDRF synthesis by NG-monomethyl-L-arginine (10(-5) M) or 4) inhibition of prostaglandin synthesis by indomethacin (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

Dietary-induced atherosclerotic lesions have increased levels of acidic FGF mRNA and altered cytoskeletal and extracellular matrix mRNA expression.

Growth factor and extracellular matrix gene expression by vessel wall cells influence the development of arterial lesions. In this study, we compared the level of acidic and basic fibroblast growth factor mRNA expression in aortic vessels from normal swine and from swine with dietary-induced vascular lesions. There was a striking increase in the level of acidic fibroblast growth factor mRNA within the lesions while the level of basic fibroblast growth factor mRNA decreased. Swine fed an atherosclerotic diet supplemented with L-arginine developed atherosclerotic plaques that also contained increased levels of acidic fibroblast growth factor mRNA. We also examined the expression level of a number of extracellular matrix and cytoskeletal mRNAs to compare the biosynthetic state of normal arteries and atherosclerotic plaques. Compared with the normal artery, the level of alpha-smooth muscle actin mRNA decreased, and there was a concomitant increase in vimentin, fibronectin and thrombospondin mRNA levels. Surprisingly, alpha 1(I), alpha 2(I) and alpha 1(III) collagen mRNA levels were decreased in the atherosclerotic lesions when compared with the normal artery. These results indicate that vascular lesion formation in hypercholesterolemic swine is accompanied by alterations in growth factor, cytoskeletal and extracellular matrix gene expression.

Animals↗

The hamstring index.

The purpose of this study was to assess the limits of hamstring tightness in 369 children by using three common tests. The straight leg-raise test averaged 100 degrees at birth, increasing to 110 degrees at age 1 year, before decreasing to 80 degrees by age 5-6 years. It then remained constant to skeletal maturity. Hamstring tightness is present if this angle is < 80 degrees in children younger than 2 years. After this age, the limit decreased steadily to plateau at 60 degrees by the age of 6 years. The popliteal angle measured the maximum 180 degrees from birth to age 2 years. This angle then decreased to average 155 degrees by age 6 years and remained steady. An angle < 125 degrees suggests significant hamstring tightness. The touching-toes test showed minimal variation between age groups averaging, 1 +/- 3 cm. Distances reached < -5 cm in children aged up to 6 years and < -15 cm in those older than 6 indicate excessively tight hamstrings. Little difference was seen between sides, although girls demonstrated less hamstring tightness. All tests showed a positive correlation with the grade of ligamentous laxity, but no association with the child's stage of puberty could be detected.

Adolescent↗