ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

This study was designed to investigate changes in contractile force, resting tension, and microsomal Ca2+uptake in isolated rat hearts perfused under conditions associated with reversible and irreversible stages of the calcium paradox phenomenon. Five minutes of reperfusion with normal medium containing 1.25 mM calcium after 5 minutes of Ca2+-free perfusion produced a marked rise in resting tension, no recovery of contractile force, and a 63% depression in microsomal Ca2+uptake. When reperfusion was carried out after 5 minutes of perfusion with 0.025 mM or greater concentrations of Ca2+, after less than 5 minutes of Ca -free exposure or after 5 minutes of varying degrees of hypothermic Ca2+-free perfusion, the increase in resting tension and decrease in contractile force development as well as microsomal Ca2+accumulation were either absent or reduced. Furthermore, reperfusion-induced increases in resting tension and decreases in microsomal Ca2+uptake also were found to be dependent on the duration of reperfusion as well as on the calcium concentration of the reperfusion medium. Microsomes isolated from control, Ca2+-free perfused or reperfused hearts were found to have similar phospholipid composition, protein profiles (SDS-polyacrylamide gel electropho-resis), and electron microscopic appearance. Whereas Ca2+-free perfusion alone had no effect on any of the parameters studied, reperfusion also depressed microsomal Ca2+-binding, Mg2+-ATPase, and Ca -stimulated ATPase activities. Changes in microsomal Ca2+uptake exhibited sigmoidal relationships with the ability of Ca2+-depleted hearts to recover their contractile force or increase their resting tension upon reperfusion. Our findings suggest that reperfusion-induced contracture and intracellular calcium overload may be associated in part with a defect in the ability of sarcoplasmic reticulum to regulate calcium.Circ Res 48:17-24, 1981

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

Right coronary reactive hyperemia and the maximal coronary vasodilator response to adenosine were examined in conscious, normal dogs and dogs with right ventricular (RV) hypertrophy. RV hypertrophy was induced by chronic (5-7 months) pulmonary artery stenosis. With RV hypertrophy, RV weight to body weight ratio rose by 70% (P< 0.001), right coronary artery blood flow (Doppler ultrasonic technique) rose from 17 ± 1 to 51 ± 5 ml/min, and RV transmural blood flow (radioactive microsphere technique) increased from 0.78 ± 0.06 to 1.62 ± 0.10 ml/min per g, while the RV endocardial: epicardial perfusion ratio decreased from 1.36 ± 0.04 to 1.10 ± 0.02. Excess blood flow debt repayment following release of a 15-second right main coronary artery occlusion was attenuated markedly (P< 0.001) to 107 ± 22% from the normal value of 325 ± 41%. Maximal coronary vasodilator capacity (to iv adenosine) was reduced in the hypertrophied right ventricle, as reflected by a lower (P< 0.05) level of maximal transmural blood flow and a higher (P< 0.02) level of minimum coronary vascular resistance per gram of hypertropied right ventricle compared to normal. During maximal coronary vasodilation, the endocardial: epicardial perfusion ratio decreased (P< 0.001) below unity in the hypertrophied right ventricle to a level (0.83 ± 0.06) significantly lower (P< 0.001) than normal (1.16 ± 0.03). Thus, the development of severe RV hypertrophy is characterized by an attenuated coronary response to acute ischemia and by a reduction in maximal coronary vasodilator capacity. We conclude that the increase in cardiac mass which results from chronic pulmonary artery stenosis is not accompanied by a proportionate increase in cross-sectional area of coronary vessels supplying the hypertrophied ventricle. Circ Res 48: 27-33, 1981

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

The effects of two doses of angiotensin II (0.025 /ig/kg per min and 0.25 /μ/kg per min) on plasma renin activity (PRA), aldosterone concentration, creatinine clearance, and sodium and potassium excretion were studied in two groups of 2- to 3-week-old lambs. The 0.025 μ/kg per min dose of angiotensin II also was studied in six adult ewes. In response to the angiotensin II infusions, PRA decreased in the newborns from baselines of 24.5 ± 2.3 ng/ml per hr (mean ± SE) and 22.9 ± 3.5 to 13.6 ± 0.8 and 13.0 ± 2.2 at 30 minutes (P< 0.01), respectively, and returned to baseline at 60 minutes; PRA decreased from 1.7 ± 0.1 to 0.95 ± 0.3 ng/ml per hr at 30 minutes (P< 0.01) in the ewe and returned to baseline at 60 minutes. Plasma aldosterone increased in the newborns from baselines of 17.4 ± 5.0 ng/ dl and 14.7 ± 3.9 to 33.1 ± 6.9 and 32.5 ± 6.3, respectively, at 15 minutes (P< 0.01) and returned to baseline at 60 minutes. Plasma aldosterone increased from 4.3 ± 0.7 to 9.2 ± 2.0 ng/dl in the ewe, and returned to baseline at 60 minutes. The change in the PRA and aldosterone responses from baseline to peak for the low and high angiotensin dose was similar in the newborn lambs and greater than in the ewe (P< 0.01). There was no change in the creatinine clearance, plasma sodium, or hematocrit. Urine sodium excretion increased from 0.16 ± 0.04 total mEq/30 min to 0.87 ± 0.27 (P< 0.05) in the newborns during the 0.25 /μ/kg per min angiotensin II infusion. We conclude that, under basal conditions, the newborn lamb has high PRA and aldosterone levels with decreased pressor and increased aldosterone and renin release responsiveness to angiotensin H compared to the adult. Circ Res 48: 34-38, 1981

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

When the propagation velocity of action potentials is modified by changing the internal resistance of a cell, cable theory predicts that the shape of the action potential upstroke should not change; changes in velocity associated with changes in the upstroke usually are attributed to changes in membrane properties. However, we observed, in normal cardiac muscle, that changes in the upstroke with velocity occur under conditions in which the membrane properties could not have changed. Propagation in atrial and ventricular muscle was studied, in which the velocity of propagation was different at different angles with respect to the cell orientation. Fast upstrokes were associated with low propagation velocities (in a direction transverse to the long cell axis) and slower upstrokes were associated with high propagation velocities (in the direction of the long cell axis). Such changes in the shape of depolarization can be accounted for by the discrete cellular nature of cardiac muscle. The recurrent discontinuities in intracellular resistance cause propagation to be discontinuous on a microscopic scale. The presence of discontinuities in intracellular resistance reverses the usual association of high velocity and high safety factor for propagation: propagation at a low velocity is actually more resistant to disturbances in membrane properties than is propagation at a higher velocity. This inverted relationship suggested that propagation could continue in a direction transverse to the long axis of the cells when block occurs in the longitudinal direction, with resultant reentrant propagation. Such prediction was confirmed in the study of the propagation of premature action potentials in atrial muscle. Circ Res 48: 39-54, 1981

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We used standard microelectrode techniques to evaluate the effects of lidocaine and quinidine on canine Purkinje fibers at normal pH (7.3) and in the presence of acidosis (pH6.9). Acidosis alone reduced resting potential, action potential amplitude, and Vmal, while increasing APD90and conduction time. Lidocaine concentrations of 6 x 10~6to 1.5 x 10~5M had minimal effect on resting potential, action potential amplitude, and Vm u at pH7.3. At pH6.9, the same lidocaine concentrations significantly reduced resting potential (3-10%), action potential amplitude (3-8%) and Vraa x (14-22%). Quinidine (6 x 10"6to 1.5 x 10~? M) reduced resting potential (3-5%), action potential amplitude (4-9%), and Vma, (19-34%) at pH 7.3. At pH6.9, quinidine produced significantly greater reductions in resting potential (4-15%), action potential amplitude (5-18%), and Vraal (22-49%). These changes were associated with much more quinidine- and lidocaine-induced prolongation of interelectrode conduction time at acidic than at normal pH. Inexcitability occurred at pH 6.9 in four of 14 experiments with 1.5 x 10~5M quinidine and in two of 10 with 1.5 X 10"5M lidocaine, and was reversed at the same drug concentration by normalizing pH.Acidosis did not alter the Vmax-resting potential relationship in either the absence or presence of antiarrhythmic agents. Furthermore, changes in ionization did not account for the alterations in electrophysiological effects of quinidine and lidocaine produced by acidosis. Our data suggest that extracellular pHchanges may modify importantly the effects of antiarrhythmic agents. Circ Res 48: 55-61, 1981

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We studied the effects of parasympathetic nerves on cerebral blood flow (CBF). The greater superficial petrosal nerve, which apparently supplies cholinergic fibers to cerebral vessels and the lacrimal gland, was sectioned on one side at the internal auditory meatus in anesthetized cats. CBF was measured with 15-/un microspheres. Section of the petrosal nerve did not alter resting CBF. In addition, electrical stimulation of the distal cut end of the petrosal nerve had no effect on total CBF. In one area of the brain, the caudate nucleus, stimulation increased blood flow from 29 ± 2 to 38 ± 2 (mean ± SE) ml/min per 100 g. Lacrimal gland blood flow increased from 42 ± 7 to 198 ± 32 ml/min per 100 g during petrosal stimulation, which indicates that the stimulus was potent. In the same experiments, CBF increased 3- to 4-fold during hypercapnia; thus, cerebral vessels were responsive to another dilator stimulus. In other experiments, petrosal nerve section did not alter the response of cerebral vessels to hypercapnia (Pco2> 50 mm Hg) or hypoxia (Po2< 34 mm Hg). We conclude: (1) there is little or no resting vasodilator tone provided to cerebral vessels by the petrosal nerve; (2) petrosal nerve stimulation has a major effect on blood flow to the lacrimal gland but does not increase CBF; and (3) petrosal nerve section has little effect on the response of cerebral vessels to hypercapnia or hypoxia. Circ Res 48: 62-69, 1981

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

In anesthetized and artificially ventilated cats, we recorded the impulse activity of 23 afferent sympathetic unmyelinated fibers with left ventricular endings, dissected from the left sympathetic rami T3 and T4. All fibers displayed a spontaneous discharge at a rate of 0.79 ± 0.2 (mean ± SE) impulses/sec. During constriction of the thoracic aorta, the discharge increased to 1.92 ± 0.2 impulses/ sec. During myocardial ischemia, produced by interruption of left main coronary artery perfusion, supplied through an extracorporeal pump, the impulse activity increased to 1.73 ± 0.3 impulses/sec. The mean latency for this excitation was 16.5 ± 1.5 sec. The intracoronary administration of bradykinin (5 and 10 ng/kg) elicited a marked increase in impulse activity that, following 5 ng/kg, reached 2.06 ± 0.2 impulses/sec, after a latency of 18 ± 2 sec and in absence of significant hemodynamic changes. Myocardial ischemia and bradykinin never revealed the existence of silent afferent fibers included in the split nerve strand. The results obtained with this experimental model indicate that the ventricular endings of these afferent sympathetic unmyelinated fibers act as "polymodal" receptors. We hypothesize that the peripheral mechanism for cardiac nociception involves intensive excitation of fibers discharging spontaneously and not recruitment of silent fibers which are purely nociceptive in function. Circ Res 48: 69-75, 1981

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

We compared the response of myocardial blood flow to exercise in normal dogs and in dogs with left ventricular hypertrophy (LVH) produced by banding the ascending aorta at 6-9 weeks of age. Blood flow was measured with 15-fim microspheres after the animals with LVH had reached adulthood when left ventricular:body weight ratios were approximately 80% greater than normal. During resting conditions, left ventricular systolic pressure was 202 ± 18 mm Hg in the dogs with LVH and 119 ± 6 mm Hg in the normal dogs (P< 0.01). Three levels of treadmill exercise which increased heart rates to 190, 230 and 260 beats/min resulted in progressive increases in left ventricular systolic pressure to a maximum of 343 ± 18 mm Hg in the dogs with LVH as compared to 165 ± 10 mm Hg in the control dogs (P< 0.01). Unlike normal dogs which showed a significant transmural perfusion gradient favoring the- subendocardium at rest [mean subendocardial: subepicardial ratio (endo:epi) = 1.25 ± 0.07], subendocardial flow did not significantly exceed subepicardial flow in the animals with LVH (mean endo: epi = 1.10 ± 0.08;P> 0.05 between normal and LVH). Myocardial blood flow increased as a direct linear function of heart rate during exericse in both groups of dogs. Exercise decreased the mean endo: epi ratio in both normal dogs (mean endo: epi = 1.10 ± 0.08 during heavy exercise;P< 0.01) and in the animals with LVH (mean endo:epi = 0.94 ± 0.03;P< 0.05), while the endo:epi ratios remained consistently less in the LVH dogs than in the normal animals (P< 0.05). The relative reduction of subendocardial flow in dogs with LVH was most apparent in the posterior papillary muscle region where the endo:epi ratio fell significantly below unity during heavy exercise (endo:epi = 0.79 ± 0.02;P< 0.01). These data demonstrate that relative blood flow to the subendocardium of the left ventricle is significantly less than normal, both at rest and during exercise, in dogs with LVH produced by supravalvular aortic stenosis. Circ Res 48: 76-87, 1981

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID

摘要:

It has been shown that intravenously injected bovine testicular hyaluronidase reduces ischemic myocardial necrosis in animal models of myocardial infarction. The mechanism for the protective effect of hyaluronidase is unknown, but it has been suggested that this enzyme depolymerizes myocardial hyaluronic acid and thus improves interstitial transport. However, biochemical data showing that intravenous hyaluronidase depolymerizes myocardial substrates are lacking. The purpose of the present study was to test the ability of hyaluronidase to depolymerize myocardial hyaluronic acid. Thirty minutes after occlusion of the left anterior descending coronary artery, nine dogs were randomized to untreated (four dogs) or hyaluronidase-treated (five dogs; 5000 National Formulary Units/kg, iv, and 0.5 and 2.5 hours post occlusion) groups. The hearts were excised 4.5 hours postocclusion and the myocardium was homogenized. Myocardial bound hyaluronidase was heat inactivated, and hyaluronic acid was extracted following protease digestion. Myocardial hyaluronic acid content was determined colorimetrically and its molecular weight was studied by Sepharose 2B gel exclusion chromatography. There was no difference in hyaluronic acid recovery or molecular weight between the ischemic anterior and non-ischemic posterior halves of the hearts of both treated and untreated dogs. Hearts of the untreated dogs contained 3.44 ± 0.32 fig hyaluronic acid/mg protein, whereas hyaluronidase-treated hearts contained only 2.06 ± 0.23 /ig hyaluronic acid/mg protein (P< 0.01). The fraction of hyaluronic acid that chromatographed with molecular weight greater than 4 x 106daltons was 73 ± 2% in untreated and only 45 ± 5% in hyaluronidase-treated animals (P< 0.001). Therefore, treatment with hyaluronidase reduces both the amount and the molecular weight of myocardial hyaluronic acid in dogs with coronary artery occlusion. Circ Res 47: 88-95, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1981

数据来源: OVID