摘要:

&NA;The purpose of this study was to investigate the factors controlling membrane permeability to potassium of smooth muscle cells from rat aorta stimulated by depolarization. The increase in42K+efflux (change in the rate constant) induced by depolarization (application of high concentrations of potassium chloride) was inhibited significantly by the calcium antagonists diltiazem and nisoldipine. Parallel inhibitory effects on contraction were observed. Diltiazem also inhibited potassium‐stimulated36Cl−efflux. The addition of 25‐150 mM KCl to normal physiologic solution stimulated42K+efflux in a concentration‐dependent manner. Diltiazem suppressed potassium‐stimulated42K+efflux approximately 90% at 25 mM KCl and approximately 40% at 150 mM KCl. The ability of nisoldipine to inhibit42K+efflux also diminished as the potassium chloride concentration was elevated. The component of efflux that was resistant to calcium antagonists probably resulted from a decrease in the electrochemical gradient for potassium. Cellular water did not change during potassium addition. Substitution of 80 and 150 mM KCl for sodium chloride produced cellular swelling and enhanced potassium‐stimulated42K+efflux compared with potassium chloride addition. The addition of sucrose to prevent cellular swelling reduced efflux response to potassium substitution toward that of potassium addition. A hypoosmolar physiologic solution produced an increase in the42K+efflux and a contracture that were both prevented by the addition of sucrose. We concluded that the depolarization‐mediated42K+efflux has three components: one is calcium dependent; a second is dependent on cellular volume; and a third is resistant to inhibition by calcium antagonists. (Circulation Research1987; 61:1‐11)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

&NA;To evaluate the effects of sex hormones on heart function and biochemistry, gonadectomy (GX) was performed in postpubertal male (M) and female (F) rats and compared with sham‐operated controls (SH). The groups were MSH; MGX; MGX replaced with testosterone 3 mg/day s.c. (MGX + T), FSH, and FGX replaced with estrogen 2 mg/day (FGX + E), progesterone 0.4 mg/day (FGX + P), estrogen and progesterone (FGX + EP), or testosterone 2 mg/day (FGX + T). Body weight was decreased in MGX and was decreased further in MGX + T. Heart weight was decreased in both MGX and MGX + T. Body weights were increased in FGX and FTX + P and were increased further in FGX + T but were normal in FGX + E and FGX + EP. Heart weights were unchanged in F groups except in FGX + T, where it was increased. Cardiac performance in perfused hearts, as measured by stroke work, ejection fraction, fractional shortening and mean velocity of circumferential fiber shortening, was decreased in MGX but was slightly increased in MGX + T. Papillary muscle studies showed increases in time to peak tension and one‐half relaxation in MGX, but these were decreased in MGX + T. Isotonic shortening studies showed decreased velocity of shortening in MGX and increased velocity in MGX + T. Heart function was significantly decreased in FGX and FGX + P compared with FSH but was similar to FSH in FGX + E and FGX + EP. FGX + T had greater stroke work and ejection fraction than FSH and FGX. Parallel changes of a lesser degree and significance was observed for velocity of circumferential fiber shortening. Gonadectomy in M and F was associated with decreases both in myosin ATPase activity and the percent of V1myosin isoenzymes, and these were prevented in males by replacement with testosterone and in females by replacement with estrogen or testosterone. The results indicate important influences of sex hormones on cardiac mass, function, and biochemistry. (Circulation Research1987;61:12‐19)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

&NA;Regional ventricular dysfunction (the stunned myocardium) persists for several hours after 15 minutes of ischemia and reperfusion in the dog. Superoxide‐radical‐induced damage appears to be one of the mechanisms of this injury. We tested whether granulocytes were a direct source of injury in the stunned myocardium in the 15‐minute ischemia dog model. Regional function during agranulocytic extracorporeal coronary perfusion (using Leukopak filters) with ischemia and reperfusion was compared with function during a second period of ischemia and reperfusion after removal of the filters (granulocytopenia). Flow reduction and reperfusion flow, preload, afterload, and inotropic stimulation were the same during agranulocytic and granulocytopenic perfusion. During agranulocytic perfusion, stunning did not occur (>100% of preischemic function during reperfusion), but when the filters were removed and about 10% of the normal granulocyte count was present, stunning occurred with only 76% return of function at 60 minutes of reperfusion (p<0.01). A second series of studied animals with extracorporeal perfusion and granulocyte replete perfusion all had less than 75% return of regional function, indicating that the agranulocytic perfusion and not the extracorporeal aspects of the experiment prevented stunning. We conclude that granulocytes are the direct source of the injury in stunned myocardium and apparently the main source of superoxide in the 15‐minute ischemia dog model. Other possible granulocyte‐related mechanisms of reperfusion injury include capillary noreflow, causing microvascular ischemia and degranulation leading to enzyme‐induced damage. (Circulation Research1987;61:20‐28)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

&NA;We investigated the roles of sodium‐calcium exchange, sarcoplasmic reticulum, and mitochondria in Caihomeostasis in cultured chick ventricular cells. Specifically, the influence of low sodium medium on contractile state, calcium fluxes, and cytosolic free [Ca] ([Ca]i) was examined. [Ca]iwas measured using fura‐2. Mean [Ca]iin control medium was 126 ± 14 nM. Exposure of cells to sodium‐free or sodium‐ and calcium‐free medium (choline‐substituted) resulted in contracture development, which returned toward the baseline level over 2‐3 minutes. The Nao‐free contracture was associated with a tenfold increase in [Ca]i(1,280 ± 110 nM) followed by a gradual decrease to a level fourfold above control [Ca]i(460 ± 58 nM). Nao‐ and Cao‐free contracture was associated with a fivefold increase in [Ca]i(540 ± 52 nM) followed by a rapid decrease to below 80 nM. Sodium‐free medium failed to produce an increase in [Ca]ior contracture in cells preexposed to calcium‐free medium, although caffeine, when subsequently added to sodium‐ and calcium‐free medium, was able to elicit a transient increase in [Ca]iand contracture. Brief, 5‐second preperfusion of cells with La3+(1 mM) or EGTA (1 mM) abolished the Nao‐free contracture and the increase in [Ca]i. In the presence of 20 mM caffeine, removal of Naoresulted in minimal changes in the resting position of the cell although45Ca uptake and [Ca]iwere increased in response to sodium‐free medium; the subsequent decrease in [Ca]iwas greatly slowed. Addition of caffeine during the relaxation phase of the sodium‐free contracture produced an additional transient contracture and transient increase in [Ca]i. Ryanodine (1 μM) abolished this effect of caffeine. Caffeine or ryanodine abolished Nao‐ and Ca‐free contracture. CCCP (2 μM), a potent oxidative phosphorylation inhibitor, did not significantly affect calcium efflux rate. In the presence of 2 μM CCCP, removal of sodium resulted in an augmented contracture signal and a rise in [Ca]i, followed by a slow decrease. We conclude that removal of extracellular sodium enhances transsarcolemmal entry of calcium via sodium‐calcium exchange, but this effect alone does not lead to the development of sodium‐free contracture. Calcium displaceable by lanthanum or EGTA appears to contribute to Nao‐free or Nao‐ and Cao‐free contracture. Studies using caffeine and ryanodine suggest that removal of Naoleads to release of calcium from the sarcoplasmic reticulum (presumably via calcium‐induced calcium release). The release calcium appears to be taken up by both mitochondria and sarcoplasmic reticulum and is in part extruded by the ATP‐dependent sarcolemmal calcium pump, causing spontaneous relaxation. (Circulation Research1987;61:29‐41)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

&NA;Synthetic atrial natriuretic factor (ANF) was either added to suffusate solutions (30 nM) or infused into the jugular vein (0.1 nanomol/min/100 g) of anesthetized rats. Steady‐state blood flow was calculated from arteriolar diameter and red blood cell velocity measurements using video microscopy in the intestinal or skeletal muscle microcirculation. Arterioles demonstrated spontaneous vasomotor tone by dilating to topical adenosine, but topical or intravenous ANF did not cause vasodilation. Either angiotensin, norepinephrine, or vasopressin was added to the suffusates in the presence or absence of a cyclooxygenase inhibitor (30 μM, meclofenamate or indomethacin) because each agonist is known to stimulate vasoactive prostanoid synthesis. In the intestine, angiotensin (500 nM) caused 40 ± 2% blood flow decreases during intravenous saline but only 23 ± 6% during intravenous ANF. Angiotensin (162 nM) and a cyclooxygenase inhibitor caused 19 ± 4% blood flow decreases but only 8 ± 5% decreases with cyclooxygenase inhibitor and topical ANF. In contrast, norepinephrine (2‐5 μM) caused vasoconstriction that was not altered by topical or intravenous ANF, either aione or in combination with cyclooxygenase inhibitors. In the spinotrapezius muscle, angiotensin (1‐2 nM) plus a cyclooxygenase inhibitor caused 40‐60% blood flow decreases but only 20‐30% decreases during intravenous or topical ANF. Topical or intravenous ANF did not alter the vasoconstriction evoked by arginine vasopressin (0.5‐1.0 nM) or by norepinephrine (40‐230 nM). Thus, 1) supraphysiologic concentrations of ANF produced no direct vasodilation in the intestinal or skeletal muscle microcirculation; 2) there was a regional difference in sensitivity to topically‐applied vasoconstrictor hormones between the two tissues; 3) ANF reduced, but did not eliminate, the vasoconstriction caused by angiotensin by a mechanism that did not involve cyclooxygenase products; and 4) ANF did not alter the vasoconstriction caused by norepinephrine or arginine vasopressin. (Circulation Research1987;61:42‐49)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

&NA;Standard microelectrode techniques were used to study the effects of a free radical generating system on action potentials recorded from guinea pig ventricular myocardium. Free radicals were generated by mixing xanthine oxidase (0.02‐0.04 μ/ml) with the superfusate‐modified Locke's solution containing purine 2.3 mM. The system was validated by demonstrating that it could reduce cytochrome C at a rate of 15.9 ± 1.5 mol/l/min. This rate was decreased to 3.0 ± 0.3 (p<0.001) in the presence of superoxide dismutase (12 mg/100 ml), and the reaction was absent if xanthine oxidase and purine were premixed for 60 minutes prior to adding cytochrome C. Superfusion of guinea pig ventricular strips with the free radical generating system (20‐30 minutes) resulted in a highly significant reduction in resting potential from − 79.3 ± 1.8 mV to −70.9 ± 1.4 mV (p<0.0001,n= 6) and in action potential amplitude from 110.9 ± 2.2 mV to 101.7 ± 4.0 mV (p<0.0001). There was an accompanying fall in maximum rate of depolarization (Vmax) from 254.1 ± 17.7 V/sec to 207.1 ± 18.6 V/sec (p<0.01) and no significant change in action potential duration. These changes were accompanied by spontaneous activity in 3 of 6 preparations and reversed after 20‐30 minutes washing in Locke's solution. They were largely abolished by adding superoxide dismutase (12 mg/100 ml) to the superfusate and completely absent if the xanthine oxidase and purine were premixed for 60 minutes before superfusing the myocardium. We conclude that the phenomena observed may contribute to the genesis of reperfusion arrhythmias. (Circulation Research1987;61:50‐54)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

&NA;The development of cardiac hypertrophy is associated with marked changes in cardiac autonomic innervation. Significant and sustained reductions of myocardial catecholamine stores and activities of tyrosine hydroxylase and dopamine &bgr;‐hydroxylase have been reported in models of acutely induced ventricular hypertrophy. Conversely, activity of choline acetyltransferase, a marker of parasympathetic nervous function, shows transient increases during the development of acute right ventricular hypertrophy. The potential physiological importance of these changes prompted us to examine a clinically more relevant model of slowly progressive ventricular hypertrophy. Application of a loose band around the pulmonary artery of weanling guinea pigs resulted in a growth‐related progressive right ventricular pressure overload. Right ventricular weight‐to‐body‐weight ratio was increased significantly and progressively at 9 and 18 weeks in banded animals (0.92 ± 0.05 and 1.31 ± 0.11 mg/g, respectively,p<0.01) compared with sham‐operated controls (0.55 ± 0.02 and 0.59 ± 0.01 mg/g, respectively) but showed no further gain at 27 weeks (1.41 ± 0.10 mg/g). Activities of tyrosine hydroxylase and dopamine &bgr;‐hydroxylase remained unchanged in all experiment groups, while right ventricular contents of norepinephrine in banded animals at 18 and 27 weeks exhibited sustained and progressive increases (2.45 ± 0.11 and 3.40 ± 0.19 μg/right ventricle, respectively) over controls (1.80 ± 0.13 and 2.40 ± 0.22 μg/right ventricle, respectively,p<0.01). The activity of choline acetyl‐transferase was markedly elevated in banded animals at 18 weeks (32.6 ± 2.7 nmol/hr/right ventricle) but returned to baseline by 27 weeks (22.8 ± 1.4 nmol/hr/right ventricle). We conclude that the time course of pressure overload is an important variable influencing sympathetic neural indexes in the hypertrophied heart. Thus, in contrast to acutely induced right ventricular hypertrophy, markers of sympathetic innervation may be preserved in severe cardiac hypertrophy provided it develops in a physiological, gradual fashion. On the other hand, transient increases of the cardiac parasympathetic marker appear to be a common feature of the development of myocardial hypertrophy produced by either acute or chronic progressive pressure overload. Our observations suggest that sympathetic‐parasympathetic interactions may vary during the development of chronic progressive cardiac hypertrophy and that these interactions may differ in chronic progressive and acute ventricular hypertrophy. (Circulation Research1987;61:55‐62)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

&NA;Infusion of &agr;‐human‐atrial natriuretic factor (&agr;‐h‐ANF) into pentobarbitol anesthetized dogs (n= 10) at 0.0025, 0.005, 0.01, and 0.3 μg/kg/min was performed to differentiate the physiologic actions of atrial natriuretic factor from its pharmacologic actions. The lowest doses of atrial natriuretic factor infusion resulted in circulating levels that were previously produced by 0‐10% saline volume expansion. At the lowest infusion rate, circulating ANF increased 31 ± 3 pg/ml, resulting in a significant increase in absolute sodium excretion, fractional excretion of sodium, and fractional excretion of lithium, and a significant decrease in urine osmolality. A greater change in circulating atrial natriuretic factor (96 ± 12 pg/ml) was required to significantly decrease right atrial pressure, cardiac output, and plasma renin activity, and to increase systemic vascular resistance and total and fractional excretion of potassium. The highest dose of atrial natriuretic factor infused was required to decrease arterial pressure and renal vascular resistance. The present study demonstrates that 1) atrial natriuretic factor is natriuretic and diuretic at physiologic concentrations; 2) at low concentrations, atrial natriuretic factor appears to decrease the whole kidney proximal tubular reabsorption of sodium and does not affect glomerular filtration rate; 3) a greater (but physiologic) change in circulating atrial natriuretic factor is required to significantly decrease cardiac output, cardiac filling pressure, and plasma renin activity than is required to significantly increase sodium excretion; and 4) a decrease in systemic arterial pressure and vascular resistance does not occur at physiologic concentrations of atrial natriuretic factor. (Circulation Research1987;60:63‐69)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

&NA;Intracellular Ca2+release and reuptake are essential for contraction and relaxation of normal heart muscle. Intracellular Ca2+transients were recorded with aequorin during isometric contraction of myocardium from patients with end‐stage heart failure. In contrast to controls, contractions and Ca2+transients of muscles from failing hearts were markedly prolonged, and the Ca2+transients exhibited 2 distinct components. Muscles from failing hearts showed a diminished capacity to restore low resting Ca2+levels during diastole. These experiments provide the first direct evidence from actively contracting human myocardium that intracellular Ca2+handling is abnormal and may cause systolic and diastolic dysfunction in heart failure. (Circulation Research1987;61:70‐76)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

&NA;To determine whether selectively altering the coronary perfusion pressure in the adjacent nonoccluded vessel has any influence on the occluded hed, the effects of alterations in the perfusion pressure of the left anterior descending coronary artery on the perfusion and function of the acutely occluded left circumflex coronary (LC) arterial bed were studied in 10 anesthetized open‐chest dogs. Radiolabelled microsphere‐assessed regional myocardial perfusion and endocardial excursion determined by two‐dimensional echocardiography were measured during control conditions prior to mid‐LC occlusion with left anterior descending coronary arterial pressure (LADP) equal to aortic pressure (AoP) (Stage 0) and to 3 randomly performed postocclusion stages. At each postocclusion stage, the perfusion territory of the occluded LC bed (area at risk) was measured in vivo using myocardial contrast two‐dimensional echocardiography. During Stage 1 (LADP = AoP), area at risk was 5.1 ± 0.9 cm2(x± 1 SD) and transmural blood flow to the LC arterial bed decreased from 0.96 ± 0.50 ml/min/g (Stage 0) to 0.16 ± 0.12 ml/min/g (p<0.01), while endocardial excursion decreased from 28.0 ± 9.0% to 2.0 ± 10.0% (p<0.01). During Stage 2 (LADP> AoP), area at risk decreased to 4.4 ± 1.0 cm2compared with Stage 1 (p<0.01), and transmural blood flow, endocardial:epicardial blood flow ratio, and endocardial excursion increased to 0.51 ± 0.39 ml/min/g, 0.64 ± 0.20, and 14 ± 6%, respectively (p<0.01). In contrast, during Stage 3 (LADP < AoP), although the area at risk increased (5.6 ± 0.7 cm2,p<0.01) and transmural blood decreased (0.10 ± 0.10 ml/min/g,p<0.01) compared with Stage 1, endocardial blood flow, endocardial:epicardial blood flow ratio, and endocardial excursion were unchanged (0.11 ± 0.16 ml/min/g, 0.52 ± 0.30, and 1.0 ± 4.0%, respectively). We conclude that significant lateral border zones exit during acute coronary ischemia, which can be influenced positively by selectively increasing the collateral driving pressure. In contrast, although the area at risk increases, when the collateral driving pressure is decreased, the endocardial blood flow and excursion in the area at risk do not further decrease. (Circulation Research1987;61:77‐85)

ISSN:0009-7330    

出版商:OVID    

年代:1987

数据来源: OVID