ISSN:0009-7330    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The present experiments were performed to determine whether digitalis-induced augmentation of cardiac receptor discharge could induce reflex reductions in renal sympathetic nerve activity. Intracoronary injection or epicardial application of acetylstrophanthidin (AS) in chloralose-anesthetized dogs caused large decreases in renal sympathetic nerve activity which were accompanied by modest decreases in heart rate and arterial pressure. Vagotomy prevented these reflex responses. Cholinergic blockade with atropine markedly attenuated the heart rate responses to AS but had little effect on the arterial pressure or renal nerve activity responses. Epicardial application of lidocaine blocked cardiac vagal afferents and the reflex responses to intracoronary AS. In sinoaortic denervated dogs, the relationships between doses of AS and mean arterial pressure, heart rate, and renal nerve activity responses were linear. Decreases in renal nerve activity were evoked by doses of AS which did not reflexly change heart rate or arterial pressure. These data show that AS can evoke reflex bradycardia, hypotension, and withdrawal of renal sympathetic nerve activity solely by augmenting the inhibitory influence of cardiac receptors with vagal afferents. This reflex effect may contribute to the changes in renal function and thus to the diuresis that occurs when heart failure is treated with digitalis. Ore Res 44: 8-15, 1979

ISSN:0009-7330    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

We studied 25 anesthetized and thoracotamized dogs before and during 5 hours of acute regional myocardial ischemia. Krypton-81m (81mKr) was infused constantly into the aortic sinuses. The myocardial equilibrium of this tracer was used to image and assess the distribution of regional myocardial perfusion using a gamma camera and digital computer. The epicardial ECG was recorded, S-T segment elevation and the loss of R and appearance of Q waves were measured, and the plasma activity of creatine kinase (CK) was determined in aortic and coronary venous blood throughout these experiments. Ten dogs underwent left anterior descending coronary artery (LAD) narrowing for 5 hours and received no drugs. Five dogs received nifedipine 13 μg/kg, and another five received 1.0 μg/kg intravenously 30 minutes after LAD narrowing. Those dogs receiving nifedipine, 13 μg/kg, showed a 30% fall in aortic pressure, a 12% rise in heart rate, and an extension of regional ischemia. The ECG showed an extension of infarct size, and CK release into the coronary vein appeared earlier than in the controls. Dogs receiving nifedipine, 1 μg/kg, showed a 12% fall in blood pressure, no rise in heart rate, an improvement in regional perfusion, and ECG signs that suggested limitation of infarct size. There also was delayed release of coronary venous CK. The effects of nifedipine on the natural history of regional myocardial perfusion, the electrocardiogram, and enzyme release from the heart were dose related and cannot be generalized. These observations warrant further clinical investigation to improve the use of this agent in man. Circ Res 44: 16-23, 1979

ISSN:0009-7330    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The effects of digoxin on monovalent cation active transport were determined in cardiac tissue obtained from dogs given inotropic, toxic, or lethal doses of digoxin. In hemodynamically monitored dogs, active uptake of the K+analogue Rb+was determined in vitro in a control myocardial biopsy, and then in serial biopsies from the same dog after the infusion of [3H]digoxin in doses sufficient to cause a sustained positive inotropic effect in the absence of toxicity, and finally after additional doses to induce overt toxicity. Nontoxic digoxin doses producing a mean increase of 20% in left ventricular (LV) dP/dt significantly reduced Rb+active transport by 25% below control values. At the onset of digoxin-induced arrhythmias, maximal LV dP/dt was 53% above control whereas active Rb+transport was reduced by 60% below baseline values (P < 0.001). Control dogs given vehicle alone showed no significant change in contractility or in monovalent cation active transport. In another group of dogs given a lethal dose of digoxin, Rb+active transport was reduced 59% below control levels at the onset of overt toxicity and was further reduced 80% below control at the time of onset of a fatal rhythm disturbance. When dogs were given high affinity digoxin-specific IgG or Fab fragments at the onset of overt toxicity, toxicity was rapidly reversed, and monovalent cation active transport increased to 51% of control at the time of restoration of sinus rhythm. Twenty-four hours after antibody reversal of arrhythmias, monovalent cation transport values approximated normal control levels. These data provide quantitative estimates of the extent of inhibition of monovalent cation transport by digoxin at inotropic, toxic, and lethal endpoints. Similar degrees of transport inhibition were present at the time of onset of digoxin-induced arrhythmias and at the time of arrhythmia reversal by digoxin-specific antibodies. Circ Res 44: 23-31, 1979

ISSN:0009-7330    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

We studied the relative rates of release of active and inactive renin by the kidney in anesthetized pigs. Renin concentration was determined in arterial and renal venous plasma as follows: (1) before and after stimulation of renin release with isoproterenol or furosemide, (2) after suppression of renin release by extracellular fluid volume expansion, and (3) after administration of propranolol or indomethacin. Inactive renin was activated by dialysis of plasma at pH 3.3 for 24 hours. Renin concentration was estimated by radioimmunoassay determination of angiotensin I after a 3-hour incubation with excess homologous renin substrate. Following isoproterenol, the release of active renin increased from 8 ± 4 (SEM) to 58 ± 34 ng/min, and inactive renin increased from 53 ± 33 to 321 ± 136 ng/min. Similarly, furosemide stimulated the release of both active and inactive renin. Both forms of renin were suppressed by propranolol or indomethacin. Although changes in renin release following volume expansion were not statistically significant, the direction of change for both forms of renin was similar. Following logarithmic conversion of the rate of release, the plot of active vs. inactive renin formed a straight line. Values for active renin as a percentage of the total renin in simultaneously drawn arterial and renal venous plasma samples were not different. Thus, under the conditions of these experiments, release of active and inactive renin appears to be controlled by similar mechanisms. Both stimulation and suppression of renin release result in parallel changes in release of the two forms. Data on relative amounts of active renin in arterial and renal venous plasma suggest that there is no systemic conversion of the two forms. Circ Res 44: 32-37, 1979

ISSN:0009-7330    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Saralasin, 10 μg/kg per min, caused an immediate rise in blood pressure in 52 of 57(91.2%) hypertensive patients. The increase in diastolic pressure averaged 18.8 ± 1.83 mm Hg (mean ± SE) in normal renin patients on a normal salt intake. This immediate pressor response was absent in only five high renin patients and, conversely, was very large in three low renin patients. Direct arterial recordings are necessary to define the response accurately; it begins in 60-90 seconds, peaks in amplitude at 2.05 ± 0.38 minutes, and subsides over the next 5 minutes in normal renin and high renin patients. The blood pressure elevation is inversely related to background plasma renin activity (r = − 0.66,P< 0.001), and also is directly, but weakly, related to 24-hour urinary sodium excretion (r =+0.29). Therefore, the amplitude of the elevation is predictably diminished by the rise in plasma renin consequent to prior sodium restriction, and also by preliminary receptor exposure to low dose nonpressor infusions of saralasin itself (0.01-0.1 μg/kg per min). Phentolamine had no effect on the response in two patients. We propose that the immediate pressor response to saralasin is related directly to the preexisting degree of vacancy of angiotensin II vascular receptors and that the initial agonistic action of the drug may prove useful in defining the angiotensin II receptor status in hypertensive diseases.Circ Res44: 38-44,1979

ISSN:0009-7330    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

We studied carotid baroreceptor reflex coronary vasoconstriction in closed-chest dogs with controlled aortic blood pressure and myocardial oxygen metabolism. The dogs were anesthetized with morphine and chloralose. Left coronary blood flow was measured by a cannula-tip flowmeter, and myocardial oxygen metabolism was calculated by measuring the arterial-coronary sinus oxygen difference. A bilateral vagotomy was performed in all animals and they were treated with propranolol. Reduction of carotid sinus pressure to 40 mm Hg caused an increase in aortic pressure that was limited to 15 mm Hg by means of a pressure-control reservoir. During carotid hypotension, heart rate and myocardial oxygen metabolism were unchanged but diastolic coronary vascular resistance increased by 21%. Intracoronary artery infusion of norepinephrine had similar effects. After interruption of the reflex are with the α-adrenergic receptor antagonist, dibozane, carotid sinus hypotension and the same increase in aortic pressure (15 mm Hg) resulted in only a 5% increase in diastolic coronary resistance. Dibozane also reduced the coronary responses to norepinephrine. It is concluded that carotid sinus hypotension results in reflex sympathetic α-receptor coronary vasoconstriction and that this reflex vasoconstriction is independent of changes in myocardial oxygen metabolism or changes in aortic pressure. Circ Res 44:44-51,1979

ISSN:0009-7330    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Tissue energy metabolism was examined in posterior (ischemic) and anterior ("control") regions of canine ventricles after 5 and 10 minutes of left circumflex coronary artery occlusion. When compared to identical regions of normal hearts, the following changes were found: (1) decreases in glycogen and phosphorylase activity in the anterior and posterior regions, (2) depressed state 3 rates of oxygen consumption of isolated mitochondria in both anterior and posterior regions, (3) shifts in optimum substrate concentrations for palmityl-CoA (+ camitine) oxidation by mitochondria in the anterior and posterior regions, and (4) decreases in the apparent zero order and first order rates of mitochondrial palmitylcarnitine production. These changes correlated with a marked decrease in developed tension in the posterior regions. Depression in tension development in the posterior regions of the heart still was present after 30-60 minutes of reperfusion following a 10-minute period of occlusion. Glycogen content in the reperfused areas was significantly decreased after 60 minutes of reperfusion when compared to normal areas and to control hearts perfused for 70 minutes. After reperfusion, mitochondrial function appeared to return toward "normal." However, the slow restoration of contraction of the ischemic area suggests that cellular mechanisms operative in vivo to restore pump function still might be abnormal. Cire Res 44: 52-61, 1979

ISSN:0009-7330    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

Renal phospholipid metabolism was studied after ischemia was induced by occlusion of the left renal artery in the rat. There was no change in the rate of cellular [14C]choline uptake after 25 or 80 minutes of ischemia. However, [14C]choline incorporation into phospholipid was two to three times greater in slices from the ischemic kidney than in slices from the contralateral control kidney. The increase occurred after 25 minutes of ischemia plus 15 minutes of reflow, and after 60 minutes of ischemia with or without reflow. When14C]choline was injected into rats after a 60-minute period of renal ischemia, the rate of incorporation into phospholipid in the ischemic kidney was almost twice that of the control kidney. These results were similar to those of the in vitro experiments. Since virtually all of the cellular phospholipids of the kidney are present in cellular membranes, renal ischemia affects membrane metabolism. The mean distribution ratio of α-aminoisobutyric acid in slices of kidneys ischemic for 60 minutes was similar to that of control slices: 4.11 ± 0.2 (SEM) VS. 4.30 ± 0.30. The normal uptake of α-aminoisobutyric acid indicates that the increased incorporation of choline is associated with functional integrity of the membrane. cire Reg 44: 62-67, 1979

ISSN:0009-7330    

出版商:OVID    

年代:1979

数据来源: OVID

摘要:

The role of locally formed cyclo-oxygenase products (endoperoxide intermediates, prostaglandins, or prostacyclins) in resistance to blood flow was studied in the hindlimbs of anesthetized dogs during rest, during exercise, and following release of inflow occlusion. Meclofenamic acid, indomethacin, or sodium meclofenamate reduced mean resting blood flows of 86, 133, and 118 ml/min to 54, 82, and 67 ml/min, respectively. Inhibitors of prostaglandin synthesis reduced the vasodilator response to arachidonic acid by 81%. In addition, prostaglandin synthesis inhibitors attenuated the hyperemic responses following inflow occlusions in the resting hindlimb. The attenuation was most marked following a l-second occlusion (74%) and progressively less following a 10-second (44%) and a 300-second (24%) occlusion. However, the portion of the total postocclusive hyperemic response attributable to prostaglandins was constant and independent of occlusion duration. Inhibition of prostaglandin synthesis did not affect the hyperemia of exercise, but reduced significantly the postocclusion hyperemia that followed the release of a l-second (63%) and a 2-second (43%) period of inflow occlusion in the exercising hindlimb; attenuation was minor following a 10-second occlusion (10%). In three of four exercising hindlimbs, the portion of the postocclusion hyperemia attributable to prostaglandins was inversely related to the duration of the occlusion. These data indicate that locally synthesized cyclo-oxygenase products, possibly prostaglandins, are important in the maintenance of blood flow in resting but not exercising muscle, contribute significantly to postocclusive hyperemia in resting and exercising hindlimbs, and mediate the hyperemia that follows occlusions of 5 seconds or less in resting and 2 seconds or less in exercising hindlimbs. cire Res 44: 67-75, 1979

ISSN:0009-7330    

出版商:OVID    

年代:1979

数据来源: OVID