摘要:

Delayed aflerdepolarizations (DADs) may develop into triggered automaticity and ventricular arrhythmias. However, the potential role of DADs in the genesis of Ischemic arrhythmias is not clear. We studied the effects of different components of severe ischemia (acidosis, hypoxia, lactate, increased potassium, and the absence of glucose) on DADs. DADs were evoked using trains of 30–60 externally applied pulses at a rate of 4–5 Hz in the presence of isoproterenol (10-7 M) or dibutyryl cyclic 3′, 5′ adenosine monophosphate (dB-cAMP, 10-3 M). Acidosis, caused by the addition of protons (pH = 6.8), increased the amplitude of DADs from 3.2 ± 0.4 to 5.9 ±0.5 mV (n = 8, p < 0.001). DADs were abolished by hypoxia (pO2 < 35 mm Hg, n= 7, p < 0.001) from control values of 3.4 ±0.3 mV. DADs were also abolished by neutral lactate (20 mM, n=7, p < 0.001) in the absence of glucose. Acidotic lactate (20 mM, pH. = 6.8), however, was unable to abolish DADs. Increasing the extracellular potassium concentration to 16.2 mM decreased DAD amplitude from 3.6 ±0.27 mV to 1.3 ± 0.1 mV (n = 5, p < 0.002) with an associated reduction of membrane potential from −86.2 ± 0.9 to − 58.6 ± 0.9 mV. The overall effect of simulated ischemia (all components tested together) was to abolish DADs (n = 8, p < 0.001), with hypoxia as the most important factor. Neither the glycolytic inhibitors iodoacetate (0.1 mM) and 2-deoxyglucose (10 mM with 10 mM pyruvate) nor the absence of glucose changed the amplitude of DADs. 2-Deoxyglucose (10 mM) in the absence of pyruvate, cyanide (0.5–2.0 mM), and dinitrophenol (0.1–1.0 mM) each abolished DADs. We interpret these findings to mean that DADs are unlikely to occur in severe myocardial ischemia.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The functional border zone is nonischemic myocardium that exhibits reduced function adjacent to an ischemic area. To determine if the functional border zone can be modified by pharmacologic interventions that alter contractility, we infused isoproterenol (0.04–0.10 μg/kg/min) or administered propranolol (2 mg/kg) during circumflex coronary occlusion in nine anesthetized, open-chest dogs. We measured systolic wall thickening on both sides of the perfusion boundary, which was delineated with myocardial blood flow (microsphere) maps constructed from small tissue samples. By fitting sigmoid curves to the composite systolic wall thickening data after coronary occlusion, we modeled the distribution of functional impairment across the perfusion boundary. Defined as the distance from the perfusion boundary to 97.5% of the nonischemic asymptote of the sigmoid fits, the functional border zone was 31± of circumference after coronary occlusion alone. Isoproterenol increased + dP/dt by 58% and augmented nonischemic systolic wall thickening without changing the lateral extent of the functional border zone (32±). Propranolol reduced + dP/dt by 24% and depressed nonischemic systolic wall thickening, but the size of the functional border zone remained limited to 28±. Within the functional border zone, wall thickening was significantly but only moderately reduced (−28%) compared with thickening in nonischemic myocardium more than 10 mm away from the perfusion boundary. The ratio of nonischemic border zone to central nonischemic area wall thickening remained the same with each intervention. We conclude that the dimensions of the functional border zone are fixed early after coronary occlusion and that inotropic interventions do not modify the extent or relative severity of nonischemic regional dysfunction.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The functional and morphologic characteristics of isolated subcutaneous resistance vessels (about 170 μm i.d.) from 15 untreated subjects with essential hypertension and 15 matched controls were examined. The vessels from the hypertensives had a 29% increase in the media-thickness-to-lumen- diameter ratio. The maximal force development to noradrenaline (NA) expressed as active pressure (an estimate of the pressure the vessels could have contracted against in vivo) was 30 % higher in vessels from the hypertensives, while active media stress (force per square unit of smooth muscle) and sensitivity to NA was not significantly different. Increased active pressure, as well as unaltered active media stress and sensitivity, was seen for vasopressin, serotonin, angiotensin II, and K+. There was, however, an enhanced leftward shift of the NA sensitivity with cocaine (an inhibitor of the neuronal amine pump) in vessels from the hypertensives [pD2(+ cocaine) and pD2(− cocaine) were 0.185 ± 0.053 and 0.040 ± 0.044, hypertensives and normotensives, respectively, p < 0.05] suggesting an abnormality of presynaptic function in essential hypertension. Furthermore, the calcium sensitivity was depressed (pD2was 4.197 ± 0.050 and 4.381 ± 0.068, hypertensives and normotensives, respectively, p < 0.05), and the rate of relaxation was faster (p < 0.05) in vessels from hypertensives, suggesting that excitation-contraction coupling might be depressed. The results suggest that the increased pressor response in essential hypertension can, to a large extent, be explained by altered vascular structure, while smooth muscle function is either unchanged or possibly depressed.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Adenosine or its synthetic analogues were topically applied to the intestinal jejunum while steady-state blood flow was calculated in submucosal arterioles using video microscopy. Blood flow increased (220 or 130% of control) with the serosal application of 10−6M N-ethyl carboxamido adenosine (NECA, A2-selective agonist) or 2-chloro adenosine (2CA, nonselective agonist) but not with cyclohexyl adenosine (CHA, A1-selective agonist). The nonselective competitive antagonist, 8-phenyl theophylline, attenuated the response evoked by NECA. The mucosal application of 10−6M CHA caused blood flow decreases (81% of control), but neither NECA nor 2CA evoked a response. These observations suggest a mucosal diffusion barrier, so the concentrations of the analogues were raised one hundredfold. Serosal 10−4M CHA or NECA caused blood flow increases, but the effects were negligible with mucosal application, suggesting that the mucosa was indeed impermeable to these compounds. The responses evoked by 10−4M 2CA were similar on the serosa or mucosa (200–220% of control), submaximal (maximum = 400% of control at 10−3M), and not antagonized by 8-phenyl theophylline or by the cellular uptake inhibitor, nitrobenzyl-6-thio guanosine. In context with earlier studies, >10−6M 2CA probably evokes vasodilation that is not entirely mediated by extracellular receptors. Serosal adenosine (10−4M) caused submaximal bood flow increases (200% of control) that were not potentiated by nitrobenzyl-6-thio guanosine or another transport inhibitor, dipyridamole. In contrast, mucosal adenosine (10−4M) had no effect on blood flow unless the transport inhibitors were present, and even then, the blood flow increase was lower than that evoked by serosal adenosine. Overall, these results suggest that 1) adenosine caused intestinal arteriolar vasodilation by intracellular and extracellular mechanisms, 2) the extracellular mechanism is mediated, in part, by A2-receptors, and 3) cellular uptake in the mucosa as well as a diffusion barrier probably restricts the passage of adenosine and its analogues from the lumen to the interstitium.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Blood flow studies were conducted in neurolept anesthetized dogs to characterize the involvement of renal nerves in ipsilateral renal vasoconstriction seen during acute elevation of renal venous pressure above 30 mm Hg. Renal blood flow was measured electromagnetically. The vasoconstrictor response was almost abolished by acute surgical denervation of the kidney, since renal vascular conductance remained unchanged during renal venous pressure elevation from 30–60 mm Hg. However, following additional α-adrenoceptor blockade or chronic renal denervation, renal vascular conductance increased progressively during renal venous pressure elevation to 60 mm Hg. The effect of acute decapsulation of kidney was studied in another group of dogs. Decapsulation induced a vasoconstriction. The decrease in renal vascular conductance observed during renal venous pressure elevation was unaffected by acute surgical denervation of decapsulated kidney, but was almost abolished following additional α-adrenoceptor blockade or chronic denervation. In decapsulated chronically denervated kidney, the increase in renal vascular conductance during renal venous pressure elevation to 60 mm Hg was still present but considerably attenuated as compared with the chronically denervated kidney with intact capsule. The renin-angiotensin system did not participate in acute vascular adjustments to renal venous stasis in intact kidney or in decapsulated acutely surgically denervated kidney. The data favor the view that neurogenic and myogenic mechanisms significantly influence the vasoconstrictor response to renal venous pressure elevation in dog kidney. The neurogenic contribution to the vasoconstrictor response comprises intrarenal and extrarenal vasoconstrictor mechanisms evoked reflexively by renal venous pressure elevation, and the myogenic contribution to the vasoconstrictor response comprises opposing vasodilator mechanisms due to increase in renal interstitial tissue pressure during renal venous pressure elevation.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We frequently study processes that alter microvascular permeability in the heart. Myocardial microvascular permeability has been estimated by determining the filtration independent reflection coefficient for β-lipoprotein (σβ-LIPO). This technique requires the measurement of myocardial lymph flow rate and the lymph-to-plasma protein concentration ratio. Unfortunately, it is a nonsurvival procedure. An index of myocardial microvascular permeability was needed that could be determined in experimental preparations without sacrificing valuable chronically instrumented animals. We attempted to relate changes in myocardial microvascular permeability and myocardial edema formation to some index of myocardial performance. In 33 acute, anesthetized dogs (with normal or disrupted myocardial microvasculatures), we measured systemic arterial pressure, systemic venous pressure, coronary sinus pressure, left ventricular pressure, the maximum rate of change in left ventricular pressure (dP/dt)max, myocardial lymph flow rate, and myocardial extravascular fluid volume. Following an increase in coronary sinus pressure, the amount of edema fluid entering the myocardium varied as a function of myocardial microvascular permeability. Further, as the heart became edematous, (dP/dt)maxchanged with respect to time [δ(dP/dt)max/δt]. Finally, a significant relation was found between σβ-LIPOand δ(dP/dt)max/δt. Since coronary sinus pressure can be elevated and δ(dP/dt)max/δt can be measured in chronic animals, this technique may be useful for evaluating myocardial microvascular permeability on a long-term survival basis.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

To characterize the pump function of the left atrium, we determined the instantaneous pressure-volume relation of the isolated supported left atrium. A physiologic after-loading system for the low-pressure atrium was created by coupling it to a real-time computer-simulated ventricle and a simulated venous impedance network via a volume servo-pump. In 10 atria loaded with such systems, multiple isochronal sets of pressure-volume data were collected from many ejecting or isovolumic contractions obtained under a constant inotropic state, and the time-varying elastance, E(t), as well as the volume-axis intercepts, V0(t), were calculated. E(t) is the ensemble of slopes, and V0(t), the volume-axis intercepts resulting from the linear regression of instantaneous pressure on instantaneous volume at multiple instants throughout the cardiac cycle. The systolic portion of the left atrial E(t) was insensitive to loading conditions, as was V0(t), which, in addition, proved to be similar to the right atrial and right ventricular V0(t) waveforms in its time dependence. These results indicate that E(t) and V0(t) adequately represent the instantaneous pressure-volume relation of the left atrium in systole irrespective of the mode of contraction. Whatever the underlying mechanism might be, the load insensitivity and similarity of the basic shape of the left atrial E(t) among different atria suggests that the characterization reflects fundamental features of left atrial contraction

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Simultaneous intraventricular pressure gradients and ejection flow patterns were measured by a multisensor catheter in 6 patients with normal left ventricular function and no valve abnormalities, at rest and in exercise. Peak measured intraventricular pressure gradients were attained very early in ejection, amounted to 6.7 ± 1.9 (SD) mm Hg at rest, and were intensified to 13.0 ± 2.3 mm Hg during submaximal supine bicycle exercise. The augmentation of the gradients during exercise was associated with a pronounced accentuation of the flow acceleration and flow at the Instant of peak gradient. At peak flow, the intraventricular gradients amounted to 5.4± 1.7 mm Hg at rest and 10.0± 1.8 mm Hg during submaximal exercise. The exercise-induced enhancement of the measured intraventricular pressure difference at the time of peak flow was underlain by an accentuation of the peak flow itself. A semiempirical fluid dynamic model for ejection was applied to the pressure gradient and simultaneous outflow rate and acceleration data to identify the contributions by local and convective acceleration effects to the instantaneous intraventricular gradient values. The peak intraventricular pressure gradient, which is attained very early in ejection, is mostly accounted for by local acceleration effects (85 ± 5% of the total). Conversely, at peak flow only convective acceleration effects are responsible for the measured pressure gradient. Thus, when inertia! effects are augmented, as in exercise and other hyperdynamic states, the intrinsic component of the total left ventricular systolic load can be substantial, even with no outflow tract or valve abnormalities. In view of the inverse force-velocity relation of the myocardium, this implies that the intrinsic component of the left ventricular load and the corresponding component of the left ventricular muscle load must be taken into account in exploring analytically the loading feedback between the total myocardial load and the acceleration, velocity and extent of shortening, which, along with end-diastolic dimensions, determine ejection flow waveforms.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Studies were initiated to investigate the effects of hypoxia on the conversion of angiotensin I (AI) to angiotensin II (AII) in microvessels of the lung. Using the technique of allografting neonatal lung tissue into the cheek pouch of normal hamsters, the microvessels of the lung, pulmonary arterioles, and venules could be visualized and manipulated by direct in vivo microscopy. The microvessels of the lung were studied 7–10 days after allografting by anesthetizing the hamster with pentobarbital (6.0 mg/100 g body weight i.p.) and then preparing the lung tissue for observation. The tissue was suffused with a Ringer's bicarbonate solution bubbled with a normal (20% O2-5% CO2-75% N2or a low (95% N2-5% CO2) oxygen mixture. After equilibration, a pulmonary arteriole or venule was selected for observation, and the vessel geometry was recorded. Then, a micropipette containing either AI or AII was positioned alongside the vessel, and the agent was delivered continuously for 2 minutes. Lumen diameter was recorded continually for 8–10 minutes. This procedure was repeated until both angiotensins were tested on pulmonary arterioles and venules under conditions of a normal and low oxygen environment. This protocol was repeated on cheek pouch microvessels that did not contain pulmonary allografts. Both AI and AII produced rapid decreases in the lumen diameters of all microvessels tested. This vasoconstriction was greater for AII, and the oxygen environment did not alter the response. Conversion of AI to AII was not altered by the oxygen environment, and the relative conversion was similar in the microvessels of the lung and cheek pouch. These studies demonstrated that acute hypoxia does not alter the conversion of angiotensin in either pulmonary or cheek pouch microvessels. Thus, an altered enzymatic activity may be restricted by the endothelial cell surface area available for conversion of angiotensin.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

We have studied the mechanical effects of fluid accumulation on the pulmonary vasculature in 28 isolated blood perfused lungs of newborn lambs. Vascular resistance in the pulmonary arteries, micro vessels, and veins was determined by micropuncture measurement of microvascular pressures, and regional distribution of blood flow in the lungs was determined using radiolabelled microspheres both before and after the development of varying degrees of hydrostatic edema. Edema was induced by raising venous pressure. During measurements, alveolar and venous pressures were kept constant at 7 and 8 cm H2O, respectively, as well as lung blood flow (540 ± 107 ml/min). All vascular pressures were referenced to the superior surface of the lung, site of all micropunctures. Active vasomotor changes were eliminated by addition of papaverine to the perfusate. Under baseline nonedematous conditions in the absence of vasomotor tone, 17% of the total pressure drop was in arteries, 41 % was in microvessels, and 42% was in veins. With the development of alveolar edema (80 ± 13% weight gain), there was no change in total or segmental vascular resistance, but after 148 ± 97% weight gain, total pulmonary vascular resistance increased by 74%. Segmental pressure drop increased in arteries by 172% and in microvessels by 132% but decreased by 22% in the venous segment. Regional distribution of blood flow remained unchanged. Possible mechanisms for increased resistance to blood flow may be compression of small arterioles and venules (<20 μm diameter) by liquid cuffs and/or occlusion of microvessels by the weight of alveolar liquid.

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID