摘要:

To investigate the mechanism underlying postischemic cardiac dysfunction (myocardial stunning), contractility and adenine nucleotide metabolism were studied in three groups of isolated perfused rabbit hearts (control, ischemic, and reperfused), whereas Ca2+uptake by the sarcoplasmic reticulum (SR) was measured in homogenates obtained from them. The hearts were Langendorff-perfused under constant pressure with Krebs-Henseleit solution at 37°C. Global normothermic ischemia was produced by closing the perfusion line. In the reperfused group, after 15 minutes of ischemia, Krebs-Henseleit solution was perfused for 10 minutes. Developed left ventricular pressure (control, 104±6.3 mm Hg) and left ventricular dP/dt (2,063±256.6 mm Hg.sec−1) were significantly decreased in reperfused hearts (left ventricular pressure, 78±5.9 mm Hg; left ventricular dP/dt, 1,339±216.3 mm Hg.sec−1). Myocardial ATP content (control, 13.6±0.98 μmol/g dry wt) decreased during ischemia (4.5±1.23 μmol/g) but was restored to control level on reperfusion (11.8±0.68 μmol/g). Maximum velocity of Ca2+uptake by the SR (Vmax) (control, 49.3±2.54 nmol.min−1.mg−1) was significantly depressed by ischemia (36.3±1.94 nmol.min−1.mg−1) but was restored to the control value after a 10-minute reperfusion (45.3±0.79 nmol.min−1.mg−1). Apparent dissociation constantKCaand the Hill coefficient for Ca2+uptake were not different between control, ischemia, and reperfusion. To test for the possible role of the SR Ca2+-release channel in the effect of ischemia and reperfusion, we measured Ca2+uptake after incubation of homogenates with 610 μM ryanodine. The changes in Vmaxcaused by ischemia and reperfusion were qualitatively similar to those observed in experiments without ryanodine (76.3±5.08, 54.0±5.08, and 69.7±2.82 nmol.min−1.mg−1for control, ischemia, and reperfusion, respectively). These results suggest an effect of ischemia on the SR Ca2+pumping without an effect on the Ca2+-release process. The recovery of Ca2+uptake during reperfusion indicates that neither an altered uptake of Ca2+by the SR nor an abnormal function of the release channels is the major cause of myocardial stunning.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We recorded direct current electrograms and local [K+]0at multiple sites and transmembrane potentials at selected sites during reperfusion after 5 minutes and 10 minutes of regional ischemia in isolated perfused pig hearts. After 10 minutes of ischemia, the incidence of ventricular fibrillation (VF) was 38%. At 80–90 seconds after reperfusion, [K+]0was 0.8 mM less than in normal tissue in half of the reperfused tissue, especially in the border zone. This was associated with TQ elevation of +4.5 mV and large peaked T waves. The latter was caused by an abrupt decrease of action potential duration in reperfused tissue, leading to a difference of up to 165 msec with normal tissue. Reperfusion VF started with a closely coupled ventricular premature beat. Activation block between reperfused and normal tissue permitted reentrant activation, leading to VF. Pretreatment with ryanodine (10−6M) and reperfusion with elevated [K+] (both of which prevent delayed afterdepolarizations) did not prevent closely coupled ventricular premature beats or VF. Five minutes of ischemia never caused VF. K+depletion and TQ elevation in the reperfused zone was less frequent and smaller (−0.4 mM and 1.8 mV, respectively). Peaked T waves did not occur, and shortening of the action potential duration was less. We conclude that extracellular K+depletion and marked action potential duration shortening in the reperfused tissue play a role in the genesis of reperfusion VF, which is caused by reentry. The closely coupled ventricular premature beat that initiates reentry is not caused by delayed afterdepolarizations but most likely by intramural reentry.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We cultured smooth muscle cells from rat renal preglomerular arterioles by injecting a suspension of iron oxide into the left ventricle, separating the arterioles magnetically, and growing cells from explants. In passaged cultures we ascertained vascular smooth muscle purity of >98% by morphology; contraction to norepinephrine and angiotensin; positive immunofluorescence staining through the sixth passage with monoclonal antibodies to smooth muscle-specific α- and γ-isoactins, myosin, and desmin; and the absence of von Willebrand factor. Angiotensin II (10−12-10−5M) induced dose-dependent DNA synthesis and proliferation of subcultured (three times) arteriolar smooth muscle cells from a growth-arrested state (p<0.01). Angiotensin II (10−5M) also induced the cells to expressc-fosmRNA. We find no previous report of culture of smooth muscle cells from renal preglomerular arterioles. Our findings also provide evidence that angiotensin II is mitogenic to arteriolar muscle cells and thus may be involved in their hyperplasia accompanying hypertension.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Pressure natriuresis may be mediated through increases in inner medullary vasa recta blood flow (QVR). By means of acute renal decapsulation to prevent increases in renal interstitial hydrostatic pressure (RIHP), the effect of increases in QVRin the presence and absence of changes in RIHP in the natriuretic and diuretic responses to increases in renal perfusion pressure (RPP) was evaluated. Blood flow in descending (QDVR) and ascending (QAVR) vasa recta was determined in the exposed papilla by fluorescence videomicroscopy in anesthetized euvolemic Munich Wistar rats. In rats with intact renal capsules (n=12), increases in RPP from 101±0.5 to 132±2.9 mm Hg caused significant increases in QDVR(from 4.7±0.9 to 5.5±0.9 nl/min,p<0.001) and QAVR(from 2.8±0.2 to 3.5±0.2 nl/min,p<0.001) in association with increases in RIHP (from 4.6±1.3 to 7.6±1.3 mm Hg,p<0.001), urine flow (from 16.2±2.6 to 20.2±3.2 μl · min−1.g kidney wt−1,p<0.01), and urinary sodium excretion (from 2.10±0.38 to 3.36±0.62 μeq.min−1.g kidney wt−1,p<0.001). Acute bilateral renal decapsulation (n=12) prevented the rise in RIHP (from 4.0±0.6 to 3.6±0.6 mm Hg), urine flow (from 13.0±2.1 to 14.2±1.5 μl · min−1.g kidney wt−1), and urinary sodium excretion (from 1.76±0.28 to 2.12±0.31 μeq.min−1.g kidney wt−1) as RPP increased from 100±0.3 to 134±2.2 mm Hg but not the increases in either QDVR(from 4.4±0.5 to 5.1±0.5 nl/min,p<0.01) or QAVR(from 2.6±0.3 to 3.3±0.3 nl/min,p<0.001). No changes in QDVR, QAVR, RIHP, urine flow, and fractional excretion of sodium were observed in a third group of time control decapsulated rats (n=7) in which RPP was held constant at 100 mm Hg. Glomerular filtration rate and total renal blood flow were stable in all three groups. These findings demonstrate that QVRincreases in response to elevations in RPP but only results in natriuresis when associated with a concomitant rise in RIHP.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Cyclosporin A (CSA) causes an acute vasoconstriction of hind limb arterial vessels. To determine the mechanism of action of CSA on the peripheral arterial bed, studies were performed on the isolated femoral artery perfused at constant flow in 61 dogs. Changes in femoral perfusion pressure reflected variations in vascular resistance. Pure powder CSA was dissolved in autologous blood and injected at doses of 1,5,10, and 20 mg. Infusions of 1 and 5 mg CSA caused nonsignificant mean increases of 4±2 mm Hg (95% confidence interval [CI], 0–8;p>0.05) and 10±4 mm Hg (95% CI, 0–21;p>0.05) in femoral perfusion pressure, with CSA blood levels in the femoral vein averaging 40±16 and 126±50 nmol/l, respectively, at the end of the injections. Infusions of 10 and 20 mg CSA caused significant increases in femoral perfusion pressure averaging of 8±3 mm Hg (95% CI, 1–14;p<0.05) and 20±4 mm Hg (95% CI, 11–29;p<0.05) in femoral perfusion pressure. CSA blood levels at the end of injections averaged 271±99 and 431±146 nmol/l, respectively, in the femoral vein. Blockade of α-adrenergic receptors with phentolamine and surgical lumbar sympathectomy decreased significantly the CSA vasoconstrictive effect in peripheral arterial vessels, with increases in perfusion pressure averaging 29±5 mm Hg before and 14±3 mm Hg after phentolamine (p<0.05) and 30±2 mm Hg before and 8±2 mm Hg after sympathectomy (p<0.05). The response to CSA was not due to cerebral stimulation, nor was it caused by stimulation of arterial chemoreceptors or intrathoracic receptors, since bolus injections of CSA in the carotid artery and in the right atrium did not cause significant changes in hind limb perfusion pressure. After lumbar sympathectomy, injections of 1, 2, and 4 μg norepinephrine caused average increases of 16±3, 36±5, and 56±6 mm Hg (p<0.05) in femoral perfusion pressure, respectively. After injection of CSA, 1, 2, and 4 μg norepinephrine caused increases of 28±3, 48±4, and 65±5 mm Hg in perfusion pressure, respectively. During CSA infusion, tyramine (50 μg/kg) caused an increase of 23±3 mm Hg (95% CI, 17–29) in perfusion pressure compared with 38±4 mm Hg (95% CI, 30–46) before CSA injection, indicating a significant difference (p<0.05). Therefore, in the dog, CSA causes an acute vasoconstriction of peripheral arterial vessels through an increase in adrenergic activity, resulting at least partly from the inhibition of neuronal norepinephrine reuptake. No central or reflex effects appear to be involved in the response.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Repeated brief episodes of total coronary artery occlusion (i.e., severe ischemia), each separated by brief periods of reperfusion, reduce infarct size after a subsequent sustained ischemia. The importance of the intensity of ischemia during these coronary artery occlusions and the role of the following transient reflow are poorly understood. Therefore, our objective was to determine whether moderate preconditioning ischemia induced by partial coronary artery stenosis (reducing coronary flow to approximately 50% of its baseline values), with or without a brief period of total reperfusion, could precondition the canine myocardium. Dogs were randomized to receive one of three preconditioning “treatments”: the R(−) group underwent 15 minutes of partial coronary stenosis without subsequent brief reperfusion (n=8); the R(+) group underwent 15 minutes of partial coronary stenosis followed by 10 minutes of full reflow (n=8); and the control group underwent no intervention (n=8). All dogs then underwent 1 hour of total coronary artery occlusion and 4.5 hours of reperfusion. Both treated groups were equally and moderately ischemic during partial stenosis: myocardial blood flow in the inner two thirds of the left ventricular wall averaged 0.25±0.05 and 0.31±0.07 ml/min per gram in the R(−) and R(+) groups, respectively (p=NS). Furthermore, all three groups were equally and severely ischemic during sustained total occlusion: myocardial blood flow in the inner two thirds of the left ventricular wall averaged 0.06±0.05, 0.05±0.03, and 0.07±0.03 ml/min/g in control, R(−), and R(+) groups, respectively (p=NS). Infarct size (expressed as percentage of the area at risk) in the R(+) group was 9.0±2.5%, which was significantly smaller (p<0.01) than the value of 22.8±5.5% observed in control animals. Stenosis followed by full reflow in the R(+) group did not, however, attenuate contractile dysfunction during the sustained total coronary artery occlusion and did not preserve function in peri-infarct tissue after reperfusion. In contrast, stenosis without reperfusion in the R(−) group did not limit infarct size (28.4±5.4%,p=NS versus control) and did not preserve wall motion during total occlusion/reperfusion. Therefore, we conclude that 1) partial coronary artery stenosis can precondition the heart, 2) complete reflow after the preconditioning ischemia is mandatory to induce myocardial protection, and 3) preconditioning with moderate ischemia does not preserve contractile function.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To investigate complementarity and competitiveness between the intrinsic and extrinsic components of the total left ventricular systolic load, hemodynamic data from 18 elderly subjects with severe aortic stenosis were analyzed before and after balloon dilation of the stenosed aortic valve. Multisensor micromanometric pressure measurements allowed calculation (simplified Bernoulli equation) of the ejection velocity and aortic input impedance spectra. Despite a 32% increase in the aortic valve area (from 0.56±0.04 to 0.74±0.05 cm2[mean±SEM],p<0.01), the peak left ventricular systolic pressure fell by only 12% (from 189±10 to 167±8 mm Hg,p<0.01). This was accompanied by an increase in the impedance at the same cardiac output. In a subset of patients (n=9) in whom the peak aortic systolic pressure rose after valvuloplasty (from 115±10 to 128±12 mm Hg,p<0.01), a 40% increase in the aortic valve area was accompanied by a marked increase in the aortic input impedance. In this subset, the steady component of the aortic input impedance increased by 24% (from 960±96 to 1,188±134 dyne.sec/ml,p<0.05), and the characteristic impedance increased by 25% (from 106±13 to 132±19 dyne.sec/ml,p<0.05). Because of an increased aortic impedance acutely following the procedure, the total left ventricular systolic load after balloon dilation of the stenotic valve was only slightly decreased despite a significant increase in aortic valve area. This represents an example of complementarity and competitiveness between the intrinsic and extrinsic components of the total systolic ventricular load. It may explain why improvement in left ventricular performance may be modest acutely following balloon aortic valvuloplasty.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To investigate the mechanisms of α1-adrenergic vascular desensitization, osmotic minipumps containing either saline (n=9) or amidephrine mesylate (AMD) (n=9), a selective α1-adrenergic receptor agonist, were implanted subcutaneously in dogs with chronically implanted arterial and right atrial pressure catheters and aortic flow probes. After chronic al-adrenergic receptor stimulation, significant physiological desensitization to acute AMD challenges was observed, i.e., pressor and vasoconstrictor responses to the al-adrenergic agonist were significantly depressed (p<0.01) compared with responses in the same dogs studied in the conscious state before pump implantation. However, physiological desensitization to acute challenges of the neurotransmitter norepinephrine (NE) (0.1 μg/kg per minute) in the presence of β-adrenergic receptor blockade was not observed for either mean arterial pressure (MAP) (30±7 versus 28±5 mm Hg) or total peripheral resistance (TPR) (29.8±4.9 versus 28.9±7.3 mm Hg/l per minute). In the presence of β-adrenergic receptor plus ganglionic blockade after AMD pump implantation, physiological desensitization to NE was unmasked since the control responses to NE (0.1 μg/kg per minute) before the AMD pumps were now greater (p<0.01) than after chronic AMD administration for both MAP (66±5 versus 32±2 mm Hg) and TPR (42.6±10.3 versus 23.9±4.4 mm Hg/l per minute). In the presence of β-adrenergic receptor, ganglionic, plus NE-uptake blockade after AMD pump implantation, desensitization was even more apparent, since NE (0.1 μg/kg per minute) induced even greater differences in MAP (33±5 versus 109±6 mm Hg) and TPR (28.1±1.8 versus 111.8±14.7 mm Hg/l per minute). The maximal force of contraction induced by NE in the presence or absence of endothelium was significantly decreased (p<0.05) in vitro in mesenteric artery rings from AMD pump dogs compared with saline control dogs. Furthermore, α1-adrenergic receptor density, as determined by [3H]prazosin binding in membrane preparations from vessels in the mesentery, was decreased (8.2±1.0 versus 18.4±1.4 fmol/mg protein,p<0.001) without any change inKdin the AMD pump dogs compared with the saline pump dogs. In aortic membranes α1-adrenergic receptor density in AMD pump dogs did not difler from saline pump dogs, but the affinity of the aortic receptors for [3H]prazosin binding was decreased (Kd0.29±0.07 versus 0.14±0.01 nM,p<0.01), and NE-induced displacement of [3H]prazosin binding demonstrated a loss of high-affinity binding sites (12±9 versus 82±2 percent,p<0.05). Thus, although endothelial mechanisms do not appear important, both autonomic reflex and biochemical mechanisms are altered by chronic αl-adrenergic receptor stimulation in the conscious dog; the altered autonomic mechanisms affect the physiological expression of desensitization, whereas separate biochemical mechanisms observed in vessels of different caliber mediate the desensitization.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The aim of this study is to quantify the porcine coronary arterial branching pattern and to use this quantification for the interpretation of flow heterogeneity. Two casts of the coronary arterial tree were made at diastolic arrest and maximal dilation. The relation between length and diameter of arterial segments was quantified, as well as the area expansion ratio and diameter symmetry of vascular nodes. These relations were used to construct computer models of the coronary arterial tree, covering diameters between 10 and 500 μm. Topology of these simulated trees was analyzed using Strahler ordering: Bifurcation ratio, diameter ratio, and length ratio were constant along orders 2–8 and equal to 3.30, 1.51, and 1.63, respectively. In each order, the number of segments per Strahler vessel was almost geometrically distributed. For the lowest orders, these predictions were confirmed by direct observations. From the network model, local pressure and flow were also predicted: Pressure fell from 90 to 32 mm Hg at the 10-μm level. The coefficient of variation (CV) of flow in individual segments was dependent on the number of perfused terminal segments (Nt) according to the fractal relation CV(Nt)∼Nt(1-D), where D is the fractal dimension (1.20). CV of flow in 1-g tissue units was predicted to be 18%. This study shows that the structure of the coronary arterial bed is an important determinant of the fractal nature of local flow heterogeneity.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The shortage of suitable donor hearts for cardiac transplantation is exacerbated by the exclusion of those that exhibit contractile malfunction during the period after brain death but before excision. We have replicated the phenomenon of brain death-induced hemodynamic deterioration in the rat in vivo. After 60 minutes of brain death (defined as the absence of electrical activity in the brain), a variety of indicators of cardiac contractile function fell by approximately 50% (thus cardiac index fell from 21±2 to 11±1 ml/min per 100 g body weight). However, once excised and perfused ex vivo, the hearts recovered a level of cardiac function that was identical to that from control animals that had not been subjected to brain death. Similarly, when hearts were excised, stored (6 hours at 4°C), and re perfused ex vivo with blood, they also recovered a functional capability identical to that of normal hearts from animals that had not been subjected to brain death. Our results question whether hemodynamic instability in brain-dead individuals is necessarily an irreversible detrimental cardiac phenomenon and whether these hearts should be excluded from transplantation.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID