摘要:

&NA;Large‐conduit coronary arteries respond to vasoactive stimuli differently than smaller coronary arterioles, but the quantitative effects of many vasoactive stimuli at various levels of the microvasculature remain unknown. To determine the site of constriction or dilation to serotonin and vasopressin in the coronary microcirculation, we studied microvascular responses in the left ventricle of anesthetized cats (n=36). To compensate for motion due to contraction of the heart, the epicardium was visualized with stroboscopic epi‐illumination controlled by a computer to flash once per cardiac cycle in mid‐diastole, making the vessels appear stationary. Serotonin (16 &mgr;g/kg/min) or vasopressin (0.5 units/min) was infused into the left atrium while maintaining aortic pressure constant with a snare on the descending aorta or inferior vena cava. Myocardial blood flow was measured with radioactive microspheres. During infusion of serotonin, aortic pressure and heart rate did not change, but myocardial perfusion increased 90±38% (mean±SEM) from a control value of 159±27 ml/min · 100 g. Arteries and arterioles larger than 90 &mgr;m constricted in response to serotonin (control 159±12 &mgr;m; percent change − 18±3; range −41 to 10%) while arterioles less than 90 &mgr;m dilated to serotonin (control 54±7 &mgr;m; percent change 22±9; range −10 to 62%). During infusion of vasopressin, aortic pressure and heart rate did not change, and myocardial perfusion decreased 16±7% (control, 147±18 ml/min • 100 g). In contrast to serotonin, infusion of vasopressin constricted arterioles less than 90 &mgr;m (control, 55±5 &mgr;m; percent change −16±3; range −27 to −2%) while arteries and arterioles larger than 90 &mgr;m did not respond or dilated modestly (control, 190±11 &mgr;m; percent change 4±2; range −29 to 43%). These responses to serotonin and vasopressin suggest that vasomotor regulatory mechanisms vary in different size arteries and arterioles in the coronary microcirculation, and the pivotal size at which differential changes occur is the 90‐&mgr;m level. (Circulation Research1989;65:343‐351)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Many studies have documented that during the development of left ventricular hypertrophy (LVH) coronary vascular growth lags behind that of cardiac muscle. To ascertain whether significant growth of coronary resistance vessels occurs with long‐standing hypertension and LVH, we studied dogs with Goldblatt (one‐kidney, one‐clip) hypertension seven months after surgery. Left ventricular minimal coronary vascular resistance (LV MCVR) was derived from adenosine‐induced maximal flow measured with 15 &mgr;m microspheres. Morphometric data were based on perfuse‐fixed hearts arrested in diastole. Hypertension and LVH were associated with a 46% increase in left ventricular weight/body weight ratio (LVH, 6.73±0.31; control, 4.62±0.30), no significant change in LV MCVR/100 g, and a reduction in total LV MCVR (LVH, 0.11±0.02 mm Hg/ml/min; control, 0.15±0.02 mm Hg/ml/min). Arterial and arteriolar wall/lumen ratios were virtually identical in the two groups. Arteriolar (lumen diameter <200 &mgr;m) numerical densities (arteriolar profiles/mm2) were also similar for the two groups even when analyzed according to lumen diameter size class and by ventricular location (epimyocardium, midmyocardium, and endomyocardium). Moreover, the relative frequency distribution of any arteriolar size class was similar for both groups. Because MCVR and arteriolar density were normal, this study provides new evidence that angiogenesis during long‐term LVH in this model is of sufficient magnitude to enable the cross‐sectional area of the coronary resistance vessels to increase in proportion to the increase in left ventricular mass. (Circulation Research1989;65:352‐359)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Using an immunological approach, we demonstrated previously that a neurofilament‐like protein is expressed in rabbit heart conduction tissue myocytes, and we proposed that these specialized cardiac muscle cells are of neuroectodermal origin. In the present study, we used the expression of the neurofilament‐like protein as a marker for identifying conduction tissue cells and studying their distribution in the developing heart. In 11‐day‐old rabbit embryos, myocytes expressing the neurofilament‐like protein were localized at the atrioventricular and the sinoatrial junctions and had a ring‐like distribution. At embryonic day 12, reactive myocytes were found also in the subendocardial layer of the dorsal ventricular wall, in continuity with labeled myocytes at the atrioventricular junction. Examination of older embryos and of neonatal and adult hearts revealed that the expression of the neurofilament‐like protein was not restricted to myocytes of conduction tissue regions, but it was also detectable in myocytes of the sinoatrial ring bundle, in scattered myocytes localized in the left sinal horn wall, and in the right atrium in proximity to atrioventricular sulcus tissue. Thus, using an intracellular marker, we show that precursors of adult atrial conduction tissue are distributed at the sinoatrial and atrioventricular junctions; at variance, ventricular conduction tissue precursors do not have a ring‐like distribution but are localized in the subendocardial layer, in continuity with the atrioventricular junctional myocytes. (Circulation Research1989;65:360‐369)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;The influence of the adrenergic system on the population of ventricular myosin isoenzymes under physiological conditions was assessed by subjection of normotensive and spontaneously hypertensive rats (SHR) to different types of physical exercise that increased the activity of the peripheral adrenergic system to varying degrees. The routines, which were 5‐6 weeks in duration, involved the mild exercise of enforced swimming (2×90 min/day), spontaneous running (daily, about 15 km/10‐12 hr) that resulted in absolute ventricular hypertrophy, and enforced running of low intensity (daily, 2×1.8 km/3 hr) but associated with marked stressors. Swimming and spontaneous running reduced the high blood pressure of SHR, whereas enforced running increased it. In both strains, the myosin isoenzymes were redistributed in the direction of V1after swimming but not after running. In SHR, therefore, reduction of pressure load seems insufficient for induction of a higher proportion of V1. The unique and, until now, unexplained effect of swimming was attributed to the pronounced activation of the peripheral adrenergic system as judged from catecholamine stores of ventricles and adrenal glands. Only swimming increased the norepinephrine content of ventricles and adrenal glands in normotensive rats. Swimming also had the strongest influence in SHR. Further evidence for the influence of the adrenergic system came from the effect of selective cardiac &bgr;‐blockade with atenolol (50 mg/kg/day). The diminished adrenergic drive of the heart reduced the proportion of V1to a greater extent in the swimming rats than in the sedentary rats. Taken together, the data demonstrate that substantial changes in adrenergic activity occur under physiological conditions associated with an altered myosin heavy‐chain expression. (Circulation Research1989;65:370‐377)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;The effects of palmitate on mechanical failure of ischemic hearts were studied in acutely (48‐hour) and chronically (6‐week) streptozotocin diabetic rats. Coronary flow was reduced by 50% in isolated working hearts perfused at a 15 cm H2O preload and 100 mm Hg afterload by the one‐way ball valve model of ischemia. Peak systolic pressure (PSP) and cardiac output (CO) decreased 40% by 4 minutes in control hearts perfused with 11 mM glucose and paced at 280 beats/min, compared with 50% in hearts from acutely diabetic rats. Addition of 1.2 mM palmitate to the perfusate accelerated failure rates, with PSP and CO decreasing 65% and 80% by 4 minutes in control and acutely diabetic rat hearts, respectively. In chronically diabetic rats, mechanical function could not be maintained in palmitate‐perfused hearts paced at 280 beats/min, even in the absence of ischemia. If these hearts were paced at 250 beats/min and subjected to ischemia, PSP and CO decreased 90% by 4 minutes, regardless of whether palmitate was added to the perfusate. Under these conditions, PSP decreased less than 10% by 4 minutes in both palmitate‐ or glucose‐perfused control hearts. Etomoxir (10−9M), a carnitine palmitoyltransferase I inhibitor, markedly decreased the rate of mechanical failure in both acutely and chronically diabetic rat hearts, in the presence and absence of palmitate. The beneficial effect of Etomoxir on mechanical function did not occur as a result of a decrease in either myocardial long chain acyl‐coenzyme A or long chain acylcarnitine levels. These data demonstrate that a reversible metabolic disorder involving fatty acids contributes to the increased susceptibility of the diabetic to myocardial ischemic injury. (Circulation Research1989;65:378‐387)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;In order to evaluate uptake kinetics of norepinephrine (NE) in different tissues, a catheterization study was performed in control subjects (n=6) and patients with enhanced sympathetic nervous activity (cirrhosis,n=12) during constant intravenous infusion of L[3H]norepinephrine ([3H]NE) for 75 minutes. In spite of a higher NE spillover from kidneys in patients compared with controls (82 vs. 49 ng/min,p<0.01), renal extraction ratios of [3H]NE were similar in the two groups (0.33 vs. 0.32, NS), and no significant change was observed during the time of infusion. In contrast, liver‐intestine extraction ratios of [3H]NE decreased significantly and equally with infusion time in patients (from 0.57 to 0.44,p<0.01) and controls (from 0.59 to 0.46,p<0.01). This was observed despite the fact that spillover of NE from this vascular bed was observed only in patients with cirrhosis and not in controls (41 vs. −5 ng/min,p<0.02). In the lower limb, net release of NE was similar in patients and controls, and extraction ratios of [3H]NE decreased almost equally with infusion time (from 0.35 to 0.30,p<0.01 and from 0.40 to 0.24,p<0.1, respectively). Whole‐body clearance of [3H]NE decreased over time in patients (−6%,p<0.01) and controls (−20%,p<0.01), but significant difference was not observed between the groups. We conclude that failure to attain a steady state with respect to [3H]NE removal was demonstrated in areas of large tissue volume relative to blood flow. This was found under the condition of high as well as low spillover of NE. Therefore, in addition to neuronal tracer rerelease, delayed distribution of the tracer in some tissues seems to be important for the changing whole‐body clearance observed. (Circulation Research1989;65:388‐395)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Sensory endings in the left ventricle are damaged by acute myocardial infarction. The goal of our experiments was to determine whether reflexes that originate in the heart are impaired by chronic myocardial infarction. Inferoposterior (n=11) or anterior (n=10) infarction was produced in dogs by ligation and intracoronary injection of rapidly hardening latex into either the proximal left anterior descending or left circumflex coronary arteries. Four weeks after infarction, the changes in renal sympathetic nerve activity induced by phenylephrine infusion, hemorrhage, and volume expansion were assessed before and after sinoaortic baroreceptor denervation. The results in infarct dogs were compared with the results in 11 sham‐operated dogs. With arterial baroreceptors intact, baroreflex sensitivity (defined as the percent change in renal nerve activity per millimeter of mercury change in mean pulmonary artery wedge pressure) was similar in all groups of dogs. Following sinoaortic denervation, dogs with anterior and inferoposterior infarction had impaired responses to volume expansion. The responses during hemorrhage were abolished in dogs with inferoposterior infarction. We conclude that chronic myocardial infarction impairs reflexes that originate in the heart in response to changes in cardiac filling pressures. (Circulation Research1989;65:396‐405)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;The effects of an acute increase in left ventricular systolic pressure and the effects of an intravenous isoproterenol infusion on myocardial (segment) lengthening rate and chamber (minor axis dimension) filling rate were examined in 12 anesthetized dogs. Measurements of left ventricular systolic pressure (by micromanometer) and of segment length and chamber dimension transients (by ultrasonic crystals) were made in variably afterloaded beats (threebeat descending aortic cross‐clamp) before and during an isoproterenol infusion that raised (+)dP/dt by 40%. During the baseline state, we found an inverse relation between the peak rate of increase in minor axis dimension [(+)dD/dt] and systolic pressure over a wide range of systolic pressures (110‐160 mm Hg) and end‐systolic dimensions (25‐40 mm); peak (+)dD/dt and end‐systolic dimension were also inversely related. During isoproterenol infusion, end‐systolic dimension fell from 29.7±3.1 to 28.0±3.1 mm and (+)dD/dt increased from 79.6±8.0 to 90.1±8.7 mm/sec; however, the slope and &lgr; intercept of the relation between (+)dD/dt and end‐systolic dimension were unchanged. Peak (+)dD/dt at a common end‐systolic dimension of 31 mm was nearly equal during baseline and isoproterenol states (64.2±6.3 vs. 65.1±6.6 mm/sec). Similar results were found using segment length transients. We interpret these data to indicate that (+)dD/dt is strongly influenced by changes in systolic pressure and dimension and that isoproterenol‐induced changes in (+)dD/dt are mediated, at least in part, through changes in systolic pressure and dimension. (Circulation Research1989;65:406‐416)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;The area postrema is a circumventricular organ that plays an important role in neurohumoral regulation of the circulation. We have developed a method to examine permeability and vascular responses of the microcirculation of the area postrema in vivo. A craniotomy was performed over the dorsal brain stem in anesthetized rats, and blood vessels to the area postrema were visualized with fluorescent microscopy. Extravasation of sodium fluorescein (MW, 386), but not 150 kDa (MW) fluorescein isothiocyanate‐dextran, occurred in the area postrema under control conditions. There was no extravasation of fluorescein or dextran in the brain stem under control conditions. Acute hypertension produced marked disruption of the barrier to 150 kDa dextran in the area postrema, compared with minimal disruption in the brain stem. We tested the hypothesis that the area postrema has greater permeability to small molecules than the brain stem and that this permeability might be accompanied by distinctive vascular responses. Topical suffusion of adenosine and ADP produced similar dose‐related dilation of arterioles to area postrema and dorsal brain stem. Topical and intravenous vasopressin produced similar dose‐related constriction of vessels to area postrema and brain stem. Electron microscopy in rats demonstrated that a barrier to horseradish peroxidase, which is absent in capillaries in the area postrema, is present in arterioles that supply the area postrema. Thus, 1) the microcirculation of the area postrema is permeable to relatively small molecules under normal conditions and is more susceptible than the brain stem to disruption of the barrier by large molecules during acute hypertension and 2) regulation of vascular tone in response to several stimuli is similar in area postrema and brain stem, despite marked differences in capillary permeability. (Circulation Research1989;65:417‐425)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

&NA;Small mesenteric arteries supplying partially isolated jejunal segments were totally occluded for 5 minutes and then released. With video microscopy, blood flow was calculated from measurements of submucosal arteriolar diameter and red blood cell velocity. For the first 30 minutes of reperfusion, the serosa was superfused with a Ringer's vehicle containing either adenosine (ADO; 10‐4M), acetylcholine (ACh; 10‐5M), or prostacyclin (PGI2; 3×10‐7M). Thereafter, the substances were removed from the suffusate, and superfusion continued with vehicle alone for an additional 10‐30 minutes. These concentrations were equieffective for causing vasodilation. During the first minute of reperfusion, blood flow increased more than 300% of baseline in all groups. Within the subsequent 30 minutes, blood flow fell to 45±3% of baseline with vehicie alone, which demonstrates the no‐reflow phenomenon. While either ADO, ACh, or PGI2was in the suffusate, vasodilation was persistent. After washout of these substances, the postocclusion blood flows were significantly higher with each treatment than with vehicle alone, which shows that each substance had a positive action. However, with ADO, blood flow was 121±7% of baseline after washout, whereas with ACh or PGI2, it was 64±10% or 69±5% of baseline after washout. This property of ADO was observed if the mucosa was superfused with a Ringer's solution or with a bile salt solution, which suggests that ADO might have similar properties in situ. After 60 minutes of reperfusion, the intestinal villi were short, thick, and edematous with epithelial necrosis and crypt degeneration. ADO attenuated most of these histological changes to a greater extent than either PGI2or ACh. Furthermore, ADO reduced a biochemical index of neutrophil infiltration; tissue myeloperoxidase concentration was increased to 169±14% of baseline with vehicle but was increased to 120±8% with ADO. Overall, these observations suggest that ADO protects the intestine from ischemia‐reperfusion injury by causing vasodilation and by inhibiting neutrophil function. The vasodilatory effect probably is a minor component because other vasodilators (ACh and PGI2) had minimal protective effects in these conditions. (Circulation Research1989;65:426‐435)

ISSN:0009-7330    

出版商:OVID    

年代:1989

数据来源: OVID