摘要:

Among the factors that might influence collateral arterial growth after arterial occlusion, the capacity to deliver blood flow in relation to metabolic need and work performance are obvious candidates. In this study in rats after superficial femoral artery ligation, we assessed collateral arterial growth (by arteriography), basal and peak limb blood flow during acetylcholine-induced vasodilation (by electronic drop counting), pressure-flow relations, and contractile power of the gastrocnemius muscle (force transduction during sciatic nerve stimulation) at intervals over 3 months after superficial femoral artery ligation. Basal and peak blood flow and muscle contractile power were clearly reduced 1 week after ligation but had returned to normal by 3 weeks. Major collateral arterial growth, however, progressed between 3 weeks and 3 months. The limb perfusion pressure-blood flow relation was still altered at 3 weeks, with blunting of the normal autoregulation, and became more normal by 3 months after superficial femoral artery ligation. Collateral arterial growth continues after blood flow adequate to maintain work performance has been restored and may reflect a response to more subtle abnormalities involving distal pressure delivery, evident in altered pressure-flow relations. (Circulation Research1992;70:546–553)

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

he heterotopically transplanted rat heart undergoes significant atrophy and a shift from V1to V3isomyosin. The purpose of this study was to pace the cardiac isograft and determine whether an increase in heart rate would attenuate the changes in cardiac mass and isoenzyme distribution. Nonpaced transplanted hearts were compared with hearts in which pacing was initiated at 7 Hz, 24 hours after transplantation, and continued for 7 days. There was a 29% decrease in myosin ATPase activity and a 22% decrease in α-myosin in the nonpaced isograft; both decreases were completely prevented by pacing. The decrease in cardiac mass was also significantly attenuated. Pacing did not alter intrinsic heart rate, systolic pressure, dP/dt, or norepinephrine concentration in the isograft. These results suggest that the adaptation in both cardiac mass and isoenzymes may be related to the rate or the rate-pressure product in the transplanted paced heart independent of left ventricular pressure, tissue catecholamines, or neural activity. (Circulation Research1992;70:554–558)

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The presence of two types of carotid sinus baroreceptors, as characterized by two different stimulus-response curves in an earlier study, suggests that each type may play a different role in the regulation of blood pressure. The discontinuous hyperbolic curve of the type I baroreceptors, marked by higher firing rates and greater sensitivity than the sigmoidal curve of type II baroreceptors, suggests that these baroreceptors would contribute more to the buffering of arterial pressure changes than the “tonically” active type II baroreceptors, which fired over greater pressure ranges and generally had spontaneous subthreshold discharge. The firing characteristics of type II baroreceptors suggest that these receptors would contribute more to regulation of tonic, baseline levels of arterial pressure. If this functional differentiation exists, the acute resetting characteristics of the two types of baroreceptors could be different. Resetting is defined as a shift in the response curve of a baroreceptor, marked by shifts in pressure threshold, in the same direction as the change in pressure to which it is exposed. Type I baroreceptors would be more likely to reset in response to a sustained acute change in pressure, since their primary role would be to prevent the initial change in pressure. However, type II baroreceptors would not reset to the acute change in pressure, since their primary role would be to maintain consistent information on the level of existing pressure. Therefore, this study was performed to examine the acute resetting ability of both types of baroreceptors by using a vascularly isolated carotid sinus preparation in the dog. Single-fiber type I and II baroreceptor recordings were obtained during slow ramp changes in sinus pressure after pulsatile conditioning at mean pressures of 50, 100, and 150 mm Hg for 15–25 minutes. Seven type I baroreceptors were also conditioned using nonpulsatile mean pressures of the same values. Firing characteristics, including pressure threshold, were determined using nonlinear regression and best-fit analysis. Type I, but not type II, baroreceptors were found to reset to acute changes in pressures. There was no significant difference in resetting of type I baroreceptors in response to pulsatile versus nonpulsatile conditioning pressures. These results indicate that the resetting abilities of the two types of baroreceptors are different and suggest the possibility of functionally different roles for each in the regulation of the cardiovascular system. (Circulation Research1992;70:559–565)

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We investigated the basis for the alterations in the intracellular potassium and sodium activity occurring in subendocardial Purkinje fibers surviving in 24-hour infarcts by examining ion activities in these Purkinje fibers removed from infarcting hearts at earlier times. Specifically, we examined intracellular potassium activity, sodium activity, and pH at 1 and 3 hours after ligation of the left anterior descending coronary artery, and we correlated the changes in ion activity with changes in maximum diastolic potential. We tested various mechanistic hypotheses relating to how the ion activity changes develop and how they affect membrane potential. We found that intracellular sodium activity in tissue removed 1 hour after ligation was on average already maximally elevated by a factor of 2 over control (19.2±2.0 mM [mean±SEM] versus 9.4±0.4 mM). Potassium activity diminished progressively over the first 24 hours (from normal of 112.0±2.7 to 61.6±2.8 mM), although half of the decrease occurred during the first hour (to 86.8±4.1 mM). Intracellular pH did not change at either 1 or 3 hours. Whereas maximum diastolic potential depolarization exceeded the calculated depolarization of the potassium equilibrium potential by a factor of 2 in 24-hour infarcts, the depolarization at 1 and 3 hours could be more nearly attributed to the loss of potassium. The change in the dependence of maximum diastolic potential on potassium equilibrium potential may be due to changes in membrane conductance caused by ionic or biochemical factors. The changes in ion activity continuously develop during the first day after ligation and may be due to multiple factors and mechanisms. (Circulation Research1992;70:566–575)

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Pre-steady-state13C nuclear magnetic resonance (NMR) spectra can provide a nondestructive probe of metabolic events associated with the physiology of intact organs. Therefore, the relation between phosphorylation state and intermediary metabolism in rabbit hearts, oxidizing [2-13C]acetate, was examined with a combination of31P and13C NMR. Multiple enrichment of the tissue glutamate pool with13C as an index of metabolic turnover within the tricarboxylic acid cycle was readily observed as a function of work load. Dynamic changes in pre-steady-state13C spectra evolved according to work load and correlated closely to respiratory rate in rabbit hearts perfused 1) under normal conditions (n=7), 2) at basal metabolic rates (20 mM KCI arrest,n=5), 3) and at heightened contractile state (10−7M isoproterenol,n= 7). The ratio of signal intensity arising from the secondary labeling sites within glutamate (C-2 and C-3) to that of the initial labeling site (C-4) reached steady state within 8.5 minutes in isoproterenol-treated hearts versus 18.5 minutes in control hearts. Work load did not affect glutamate concentration or fractional enrichment at the C-4 position, although an unlabeled fraction of glutamate persisted. Arrested hearts displayed slowed evolution of steady-state13C enrichment with increased contributions from anaplerotic sources for tricarboxylic acid intermediate formation (32%) as compared with control (9%). Thus, the response of mitochondrial dehydrogenase activity to the demands of cardiac performance is likely to influence the recruitment of anabolic sources supplying the tricarboxylic acid cycle. In contrast to changes in13C NMR spectra, relative high-energy phosphate levels from31P spectra were similar at all work loads, with no apparent differences in free ADP, as indicated by similar phosphocreatine to ATP ratios (2.1–2.3). These findings suggest that regulation of respiratory activity is mediated by changes in the rate of reducing equivalent generation from substrate oxidation. (Circulation Research1992;70:576–582)

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The hypothesis that ventricular in-plane tensile wall stresses are the major determinant of systolic coronary flow was investigated in this study. We measured coronary artery inflow in the maximally vasodilated bed of the isolated beating septum (n= 10) during two modes of contraction characterized by markedly different levels of developed in-plane stress. An increase in contractility was induced by changing from the control steady-state pacing state to a postextrasystolic potentiated state induced by a modified rapid pacing protocol. Over a range of increments of passive stretch, the systolic flow impediment versus the diastolic wall strain was described by an inverse linear relation. Despite the differences in developed in-plane wall stresses between the two modes of contraction (p<0.001), the slope and intercept of these relations in both the control and potentiated states were not different for the low versus high developed stress modes. The systolic flow impediment versus diastolic wall strain relation for the potentiated beats, compared with the control beats, was characterized by an increase in the intercept in both the low developed stress beats (p<0.05) and the high developed stress beats (p<0.05). These data indicate that the impediment to coronary flow during systole is not primarily determined by systolic myocardial in-plane tensile wall stresses but rather by the contractile state of the muscle. (Circulation Research1992;70:583–592)

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Vascular smooth muscle cells (VSMCs) proliferate in response to arterial injury. Recent findings suggest that, in addition to platelet-derived growth factors, growth factors from inflammatory cells and endothelial cells at the site of injury may contribute to VSMC proliferation. We hypothesized that a common mechanism by which endothelial cells and inflammatory cells stimulate VSMC growth could be the active oxygen species (i.e., O2, H2O2, and ·OH) generated during arterial injury. Using xanthine/xanthine oxidase to generate active oxygen species, we studied the effects of these agents on VSMC growth. Xanthine/xanthine oxidase (100 μM xanthine and 5 microunits/ml xanthine oxidase) stimulated DNA synthesis in growth-arrested VSMCs by 180% over untreated cells. Administration of the scavenging enzymes superoxide dismutase and catalase demonstrated that H2O2was primarily responsible for xanthine/xanthine oxidase-induced VSMC DNA synthesis. H2O2directly increased VSMC DNA synthesis and cell number (maximal at 200 μM) but decreased DNA synthesis of endothelial cells and fibroblasts. This effect was protein kinase C independent: sphingosine, a potent protein kinase C inhibitor, failed to block H2O2-induced VSMC DNA synthesis. H2O2(200 μM) stimulated c-mycand c-fosmRNA levels by fourfold and 20-fold, respectively, as compared with quiescent levels. In contrast to DNA synthesis, H2O2induction of c-mycand c-fosmRNA was primarily protein kinase C dependent. These findings show that H2O2specifically increases VSMC DNA synthesis and suggest a role for this oxidant in intimal proliferation, especially after arterial injury. (Circulation Research1992;70:593–599)

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Neomammalian and paleomammalian (limbic) brain structures control different behaviors and the autonomic support specific to each. Both neural systems are involved in cardiovascular disorders. Our previous studies showed that bilateral cryoblockade of a neomammalian structure (the frontal lobes) reduces blood pressure elevations in experimental hypertension and prevents lethal arrhythmogenesis in experimental myocardial infarction. Other studies showed that bilateral lesions in a paleomammalian structure (amygdala) also reduce the blood pressure elevations. Thus, we hypothesized that cryoblockade of the amygdala would prevent lethal arrhythmogenesis. We found that cooling of cryoprobes implanted bilaterally in the amygdala prevented ventricular fibrillation in five of eight pigs during a 20-minute period of reversible myocardial ischemia, whereas cryoblockade in structures surrounding the amygdala (five pigs), unilateral cryoblockade in the amygdala (two pigs), or sham operations (three pigs) did not prevent ventricular fibrillation (p<0.003). In two of the five pigs with amygdaloid blockade, the cooling was reversed at 20 minutes while the coronary occlusion continued (24 hours), and still ventricular fibrillation did not occur. In all other cases, ischemia was reversed at 20 minutes so that the heart could recover; this enabled histochemical documentation that the heart was normal at the time(s) ischemia was induced, and it allowed within-subject control experiments. Amygdaloid cryoblockade produced a small but significant increase in heart rate (10 beats per minute) without a change in blood pressure. We conclude that the paleomammalian brain, like its neomammalian counterpart, mediates brain effects on fatal arrhythmogenesis. (Circulation Research1992;70:600–606)M

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Continuous production of endothelium-derived nitric oxide (NO) in peripheral vessels has been shown to modulate vascular resistance and blood pressure. NO is also formed in the brain upon activation of glutamate receptors, which are thought to mediate central autonomic reflexes. In the present study we assessed whether NO plays a role in central autonomic regulation. For this, we have investigated the effects ofNG-methyl-l-arginine (NMA), a selective inhibitor of NO synthesis from l-arginine, on sympathetic renal nerve activity (RNA), blood pressure, and heart rate in the anesthetized rat. NMA elicited a dose-dependent sustained increase in blood pressure (approximately 20 and 30 mm Hg, 5 minutes after 10 and 50 μmol/kg i.v., respectively). Heart rate and RNA decreased transiently (15 beats per minute and 40%, respectively); RNA subsequently increased (100%) while blood pressure remained elevated. Baroreceptor deafferentation markedly altered these responses to NMA; the transient decreases in heart rate and RNA were abolished, whereas the increases in RNA and blood pressure were significantly potentiated. After spinal C-1-C-2 transection, there was no increase in RNA, and blood pressure increased to a smaller extent. l-Arginine blocked the NMA-induced increases in blood pressure and RNA. Thus, in addition to modulating vascular resistance by a peripheral action, NO may also play a role in the central regulation of sympathetic tone. (Circulation Research1992;70:607–611)

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

ATP-sensitive K+channels with a conductance of 30 pS in smooth muscle cells of porcine coronary artery were found to be highly active in the intact cell-attached patch configuration when the pipette contained a physiological concentration of Ca2+(>10−4M). In the inside-out configuration, these channels were activated by extracellular Ca2+and blocked by cytosolic ATP and glibenclamide. Endothelin applied to the pipette specifically blocked these channels in a concentration-dependent manner in the cell-attached configuration (half-maximal inhibition, 1.3×10−9M). A K+channel opener, nicorandil, activated these channels even in the presence of 10−8M endothelin. In the whole-cell current-clamp method, the cell membrane was depolarized by endothelin and then repolarized by nicorandil. The membrane depolarization is closely related to contraction of smooth muscle cells. These results suggest that the ATP-sensitive K+channels are important in controlling the vascular tone of the coronary artery and that endothelin can increase vascular tone by blocking these channels. (Circulation Research1992;70:612–616)

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID