Recent studies have established a major role for oxygen-derived free radicals in post ischemic tissue injury to the intestine. During ischemia, there appears to be a calcium-triggered, protease-dependent conversion of the native xanthine dehydrogenase to a superoxide-producing xanthine oxidase. The catabolic degradation of ATP during ischemia provides an oxidizable substrate, hypoxanthine. On reperfusion, molecular oxygen is resupplied and a burst of superoxide production ensues, resulting in extensive tissue damage. The same mechanism appears to occur in myocardial ischemia. Xanthine dehydrogenase rapidly converts to the oxidase during nonperfusion in the rat heart. In the isolated perfused working rat heart model, 40 min of anoxia followed by reoxygenation results in substantial release of creatine kinase. The release of creatine kinase is blocked almost completely by pretreatment of the rats with allopurinol, a specific inhibitor of xanthine oxidase.
{"title":"Free radicals and myocardial ischemia. The role of xanthine oxidase.","authors":"J M McCord, R S Roy, S W Schaffer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recent studies have established a major role for oxygen-derived free radicals in post ischemic tissue injury to the intestine. During ischemia, there appears to be a calcium-triggered, protease-dependent conversion of the native xanthine dehydrogenase to a superoxide-producing xanthine oxidase. The catabolic degradation of ATP during ischemia provides an oxidizable substrate, hypoxanthine. On reperfusion, molecular oxygen is resupplied and a burst of superoxide production ensues, resulting in extensive tissue damage. The same mechanism appears to occur in myocardial ischemia. Xanthine dehydrogenase rapidly converts to the oxidase during nonperfusion in the rat heart. In the isolated perfused working rat heart model, 40 min of anoxia followed by reoxygenation results in substantial release of creatine kinase. The release of creatine kinase is blocked almost completely by pretreatment of the rats with allopurinol, a specific inhibitor of xanthine oxidase.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14116922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The ultrastructure and electrophysiological properties of ventricle cells from newborn rats were studied before and after explantation. The cultured cells were dissociated either with trypsin or with collagenase, the latter enzyme being used with and without stirring with a magnetic bar. The explanted cells were studied 10 hr and 48 hr or more after explantation. At 10 hr after explantation, the cells exhibited fast-rising action potentials, but their myofibrils were disorganized, except for stirred collagenase-dispersed cells, which were also depolarized and inexcitable. At 2 days and later after explantation, all preparations had well-defined sarcomeres and myofibrils oriented in parallel similar to the ventricle before explantation, but the cells showed slow-response action potentials together with spontaneous activity. These findings suggest that the disorganization of myofibrils does not reflect damage to the surface membrane. Moreover, collagenase seems more damaging to the cells than trypsin under similar conditions (comparable periods of mechanical stirring), especially 10 hr after explantation.
{"title":"Influence of explantation procedure on the electrical and morphological properties of cultured neonatal rat ventricle cells.","authors":"B Fermini, O F Schanne, J S Hugon","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The ultrastructure and electrophysiological properties of ventricle cells from newborn rats were studied before and after explantation. The cultured cells were dissociated either with trypsin or with collagenase, the latter enzyme being used with and without stirring with a magnetic bar. The explanted cells were studied 10 hr and 48 hr or more after explantation. At 10 hr after explantation, the cells exhibited fast-rising action potentials, but their myofibrils were disorganized, except for stirred collagenase-dispersed cells, which were also depolarized and inexcitable. At 2 days and later after explantation, all preparations had well-defined sarcomeres and myofibrils oriented in parallel similar to the ventricle before explantation, but the cells showed slow-response action potentials together with spontaneous activity. These findings suggest that the disorganization of myofibrils does not reflect damage to the surface membrane. Moreover, collagenase seems more damaging to the cells than trypsin under similar conditions (comparable periods of mechanical stirring), especially 10 hr after explantation.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14119805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, we demonstrate the in vivo labeling by [3H]nitrendipine ([3H]NTD) of peripheral tissues and the brain in Sprague-Dawley rats. Specific binding is decreased in a dose-dependent manner by nifedipine, with a mean inhibitory dose of 2-10 mg/kg (i.p.). Thin-layer chromatography of the particulate-bound radioactivity reveals that the predominant tritiated drug bound in the left ventricle and the cerebral cortex is [3H]NTD, whereas metabolites constitute the main species in the liver. Peak radioactivity is seen at 15 min following an intravenous injection of [3H]NTD. Highly perfused tissues such as the heart, brain, and lung have significant [3H]NTD binding. In contrast to previously reported in vitro studies, [3H]NTD binding is low in the aorta, skeletal muscle, and ileum. This in vivo animal model is suitable for pharmacokinetic and physiological studies of the calcium channel in intact animals.
{"title":"Identification of calcium-channel receptors in intact animals.","authors":"W R Roeske, H R Lee, H I Yamamura, H Schoemaker","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In this study, we demonstrate the in vivo labeling by [3H]nitrendipine ([3H]NTD) of peripheral tissues and the brain in Sprague-Dawley rats. Specific binding is decreased in a dose-dependent manner by nifedipine, with a mean inhibitory dose of 2-10 mg/kg (i.p.). Thin-layer chromatography of the particulate-bound radioactivity reveals that the predominant tritiated drug bound in the left ventricle and the cerebral cortex is [3H]NTD, whereas metabolites constitute the main species in the liver. Peak radioactivity is seen at 15 min following an intravenous injection of [3H]NTD. Highly perfused tissues such as the heart, brain, and lung have significant [3H]NTD binding. In contrast to previously reported in vitro studies, [3H]NTD binding is low in the aorta, skeletal muscle, and ileum. This in vivo animal model is suitable for pharmacokinetic and physiological studies of the calcium channel in intact animals.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14121500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transmembrane action potentials (APs) of electrically paced right-atrial tissue obtained from 38 patients of corrective open-heart surgery were analyzed. Two types of APs could be found. The APs of 20 patients (group I) were similar to those of other laboratory mammals. The average resting potential (RP) and the amplitude and maximum rate of rise of phase 0 of APs (Vmax) were -75 mV, 86 mV, and 152 V/sec, respectively, only the repolarization phase being more prolonged than that of other mammalian APs. Epinephrine (5.8 X 10(-6) mole/liter) increased the amplitude of APs and prolonged the plateau phase, producing odd-looking, humped APs. Prostacyclin-Na (6.7 X 10(-7) and 8.7 X 10(-6) mole/liter) increased Vmax. Celluline-A (a biological Ca-complex obtained from frog skin) increased both Vmax and the amplitude of APs and, similar to epinephrine, prolonged the plateau phase. In group I, postoperative arrhythmias occurred in only 1 of the 10 patients. APs obtained from another 18 preparations (group II) were characterized by low RP (-55 mV), small amplitude of AP (59 mV), slow rate of rise of AP (less than 10 V/sec), and very prolonged repolarization. This type of APs can be referred to as slow-response APs. Neither epinephrine, prostacylin-Na, nor celluline-A modified the characteristics of these slow-response APs. In group II, postoperative arrhythmias could be observed in 8 of the 10 patients.
本文分析了38例心脏直视手术右心房电节律组织的跨膜动作电位(APs)。可以发现两种类型的ap。20例患者(ⅰ组)的APs与其他实验哺乳动物相似。ap的平均静息电位(RP)为-75 mV, 0相幅度和最大上升速率(Vmax)为- 86 mV,最大上升速率为152 V/sec,仅复极相较其他哺乳动物ap延长。肾上腺素(5.8 X 10(-6) mol /l)增加ap振幅,延长平台期,产生奇怪的驼峰ap。前列环素- na (6.7 X 10(-7)和8.7 X 10(-6) mol /l)增加Vmax。纤维素- a(一种从青蛙皮肤中提取的生物钙复合物)增加了Vmax和APs的振幅,并且与肾上腺素相似,延长了平台期。在I组,10例患者中只有1例发生术后心律失常。从另外18种制剂(II组)获得的AP具有低RP (-55 mV)、小AP振幅(59 mV)、慢AP上升速率(小于10 V/sec)和极长复极化的特点。这种类型的ap可以称为慢响应ap。肾上腺素、前列环素- na和纤维素- a都不能改变这些慢反应ap的特征。II组10例患者中有8例出现术后心律失常。
{"title":"Physiological and pharmacological analysis of transmembrane action potentials of human atrial fibers.","authors":"V Kecskeméti, K Kelemen, F Solti, Z Szabó","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Transmembrane action potentials (APs) of electrically paced right-atrial tissue obtained from 38 patients of corrective open-heart surgery were analyzed. Two types of APs could be found. The APs of 20 patients (group I) were similar to those of other laboratory mammals. The average resting potential (RP) and the amplitude and maximum rate of rise of phase 0 of APs (Vmax) were -75 mV, 86 mV, and 152 V/sec, respectively, only the repolarization phase being more prolonged than that of other mammalian APs. Epinephrine (5.8 X 10(-6) mole/liter) increased the amplitude of APs and prolonged the plateau phase, producing odd-looking, humped APs. Prostacyclin-Na (6.7 X 10(-7) and 8.7 X 10(-6) mole/liter) increased Vmax. Celluline-A (a biological Ca-complex obtained from frog skin) increased both Vmax and the amplitude of APs and, similar to epinephrine, prolonged the plateau phase. In group I, postoperative arrhythmias occurred in only 1 of the 10 patients. APs obtained from another 18 preparations (group II) were characterized by low RP (-55 mV), small amplitude of AP (59 mV), slow rate of rise of AP (less than 10 V/sec), and very prolonged repolarization. This type of APs can be referred to as slow-response APs. Neither epinephrine, prostacylin-Na, nor celluline-A modified the characteristics of these slow-response APs. In group II, postoperative arrhythmias could be observed in 8 of the 10 patients.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"15001957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tension, dT/dt, and extracellular free [Ca] [( Ca]0) were continuously measured in isolated rabbit right papillary muscles at 28 degrees C. Double-barreled Ca-selective microelectrodes incorporating Simon's neutral Ca exchange resin (ETH-1001) were used to monitor [Ca]0. Decreases of [Ca]0 were seen during the course of single twitches, before the development of significant tension. This depletion of Ca0 probably represents Ca influx into the cells from the extracellular space. The magnitude of this Ca0 depletion is decreased by Co, verapamil, long rest intervals, and reduction of [Ca]0. The magnitude is increased by catecholamines, reduction of [Na]0, caffeine, continued pacing, and elevation of [Ca]0. After 3-min rest, stimulation (0.5-1 Hz) produces a biphasic tension response (larger first beat, small second beat, and monotonic rise to control). Caffeine (5 mM) changes the pattern after rest to a monotonic increase. Ca influx increases monotonically in both cases. Addition of 20 mM Co during the rest reduces tension of all beats by similar amounts in the presence of caffeine. In the absence of caffeine, Co has a much weaker effect on the first beat than on subsequent beats. The results suggest that caffeine inhibits an intracellular component of activator Ca that is more important after a rest interval, but that Ca influx becomes increasingly more important during continued pacing under the conditions used here.
{"title":"The role of Ca influx in cardiac muscle excitation-contraction coupling. Assessment by extracellular Ca microelectrodes.","authors":"D M Bers, D B Merrill","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Tension, dT/dt, and extracellular free [Ca] [( Ca]0) were continuously measured in isolated rabbit right papillary muscles at 28 degrees C. Double-barreled Ca-selective microelectrodes incorporating Simon's neutral Ca exchange resin (ETH-1001) were used to monitor [Ca]0. Decreases of [Ca]0 were seen during the course of single twitches, before the development of significant tension. This depletion of Ca0 probably represents Ca influx into the cells from the extracellular space. The magnitude of this Ca0 depletion is decreased by Co, verapamil, long rest intervals, and reduction of [Ca]0. The magnitude is increased by catecholamines, reduction of [Na]0, caffeine, continued pacing, and elevation of [Ca]0. After 3-min rest, stimulation (0.5-1 Hz) produces a biphasic tension response (larger first beat, small second beat, and monotonic rise to control). Caffeine (5 mM) changes the pattern after rest to a monotonic increase. Ca influx increases monotonically in both cases. Addition of 20 mM Co during the rest reduces tension of all beats by similar amounts in the presence of caffeine. In the absence of caffeine, Co has a much weaker effect on the first beat than on subsequent beats. The results suggest that caffeine inhibits an intracellular component of activator Ca that is more important after a rest interval, but that Ca influx becomes increasingly more important during continued pacing under the conditions used here.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13724539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1985-01-01DOI: 10.1007/978-1-4757-1287-2_7
E Carafoli
Three systems mediate the fluxes of calcium across heart sarcolemma: the slow calcium channel (influx), the ATP-dependent calcium pump (efflux), and the Na+/Ca2+ exchanger (efflux, but possibly also influx). Calmodulin regulates the pumping ATPase by direct interaction and also by activating a protein kinase. The Na+/Ca2+ exchanger is modulated by calmodulin via a phosphorylation-dephosphorylation cycle. Both the kinase and the phosphatase are membrane-bound and calmodulin-sensitive. The kinase has higher Ca2+ affinity than the phosphatase.
{"title":"Calmodulin in the regulation of calcium fluxes in cardiac sarcolemma.","authors":"E Carafoli","doi":"10.1007/978-1-4757-1287-2_7","DOIUrl":"https://doi.org/10.1007/978-1-4757-1287-2_7","url":null,"abstract":"<p><p>Three systems mediate the fluxes of calcium across heart sarcolemma: the slow calcium channel (influx), the ATP-dependent calcium pump (efflux), and the Na+/Ca2+ exchanger (efflux, but possibly also influx). Calmodulin regulates the pumping ATPase by direct interaction and also by activating a protein kinase. The Na+/Ca2+ exchanger is modulated by calmodulin via a phosphorylation-dephosphorylation cycle. Both the kinase and the phosphatase are membrane-bound and calmodulin-sensitive. The kinase has higher Ca2+ affinity than the phosphatase.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13722076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Isolated papillary-muscle preparations from the cat and rabbit were used to study the phenomenon of reoxygenation contracture and whether is is amenable to intervention independently of the preceding hypoxic insult. Reduction of extracellular Ca2+ to "0" mM abolished reoxygenation contracture, but subsequent replacement of Ca2+ resulted in severe contracture and death due to the "calcium paradox." Lowering of Ca2+ to 0.125 mM and its stepwise replacement to 2.5 mM resulted in no contracture with good mechanical recovery. Gradual reoxygenation, Mg2+ (30 mM), Mn2+ (8 mM), or H+ (pH 6.5) ions, or diltiazem (10(-4) M) delayed but did not prevent the development of contracture and contractile failure. Unlike diltiazem, verapamil (10(-4) M) and lidoflazine (2 X 10(-5) M) did not significantly affect the contracture.
{"title":"Myocardial reoxygenation damage. Can it be circumvented?","authors":"S P Chappell, M J Lewis, A H Henderson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Isolated papillary-muscle preparations from the cat and rabbit were used to study the phenomenon of reoxygenation contracture and whether is is amenable to intervention independently of the preceding hypoxic insult. Reduction of extracellular Ca2+ to \"0\" mM abolished reoxygenation contracture, but subsequent replacement of Ca2+ resulted in severe contracture and death due to the \"calcium paradox.\" Lowering of Ca2+ to 0.125 mM and its stepwise replacement to 2.5 mM resulted in no contracture with good mechanical recovery. Gradual reoxygenation, Mg2+ (30 mM), Mn2+ (8 mM), or H+ (pH 6.5) ions, or diltiazem (10(-4) M) delayed but did not prevent the development of contracture and contractile failure. Unlike diltiazem, verapamil (10(-4) M) and lidoflazine (2 X 10(-5) M) did not significantly affect the contracture.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"15103907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F Yamamoto, A S Manning, M V Braimbridge, D J Hearse
The ability of nifedipine, verapamil, and diltiazem to enhance cardioplegic protection has been assessed using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest. With normothermic ischemia (30 or 35 min at 37 degrees C), the addition of these compounds enhanced the protective properties of the St. Thomas' cardioplegic solution. All these compounds showed bell-shaped dose-response characteristics, with the optimal concentrations in terms of functional recovery and enzyme leakage of verapamil being 1.0 mumole/liter; nifedipine, 0.075 mumole/liter; and diltiazem, 0.5 mumole/liter. However, under conditions of hypothermia (150 or 180 min at 20 degrees C), none of these compounds improved postischemic functional recovery, although there was some reduction in enzyme leakage. From these results, further experiments were undertaken to investigate the relationship between calcium antagonists and temperature. Verapamil improved functional recovery at 34, 31 and 29 degrees C, but not at 27, 25, and 20 degrees C. These results suggest a common site of action between hypothermia and calcium antagonists in promoting functional recovery after ischemia.
{"title":"Calcium antagonists and myocardial protection during cardioplegic arrest.","authors":"F Yamamoto, A S Manning, M V Braimbridge, D J Hearse","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The ability of nifedipine, verapamil, and diltiazem to enhance cardioplegic protection has been assessed using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest. With normothermic ischemia (30 or 35 min at 37 degrees C), the addition of these compounds enhanced the protective properties of the St. Thomas' cardioplegic solution. All these compounds showed bell-shaped dose-response characteristics, with the optimal concentrations in terms of functional recovery and enzyme leakage of verapamil being 1.0 mumole/liter; nifedipine, 0.075 mumole/liter; and diltiazem, 0.5 mumole/liter. However, under conditions of hypothermia (150 or 180 min at 20 degrees C), none of these compounds improved postischemic functional recovery, although there was some reduction in enzyme leakage. From these results, further experiments were undertaken to investigate the relationship between calcium antagonists and temperature. Verapamil improved functional recovery at 34, 31 and 29 degrees C, but not at 27, 25, and 20 degrees C. These results suggest a common site of action between hypothermia and calcium antagonists in promoting functional recovery after ischemia.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"15103994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1985-01-01DOI: 10.1007/978-1-4757-1287-2_22
D C Gadsby
Moderate changes in the size of the outward (hyperpolarizing) current that is generated directly by the electrogenic Na/K exchange pump in the surface membrane of cardiac Purkinje fibers can cause substantial alterations in the shape of the action potential, in the level of the diastolic potential, or of the resting potential of quiescent cells, or in the rate of firing of spontaneously active preparations. Transient increments in Na/K pump current, of suitable magnitude, can be elicited experimentally in small canine Purkinje fibers by causing a transient increase in their intracellular Na concentration, [Na]i, and, thereby, a transient increase in the rate of electrogenic Na extrusion. Two techniques were used to increase [Na]i: in the first, the rate of Na extrusion from the cells was temporarily reduced by omitting K ions from the bathing fluid for short periods of time, in the second, the rate of Na entry into the cells was temporarily increased by electrically stimulating the preparations rapidly (e.g., greater than or equal to 2 Hz) for brief periods. After the extracellular K concentration was restored, or after electrical stimulation was stopped, respectively, use of a two-microelectrode voltage-clamp technique allowed the resulting increments in pump current to be measured directly, as changes in holding current. Increments in pump current elicited by these two methods in the same preparation decline with the same exponential time-course. In preparations stimulated electrically at a regular, low rate (e.g., less than or equal to 1 Hz) both methods of temporarily stimulating the Na/K pump cause a marked, transient reduction in the duration of the action potential. A closely similar reduction in action-potential duration to that observed during enhanced pump activity can be elicited by injecting, from an external source, a steady hyperpolarizing current of magnitude similar to that of the increment in pump current recorded in the same preparation under voltage clamp.
{"title":"Influence of Na/K pump current on action potentials in Purkinje fibers.","authors":"D C Gadsby","doi":"10.1007/978-1-4757-1287-2_22","DOIUrl":"https://doi.org/10.1007/978-1-4757-1287-2_22","url":null,"abstract":"<p><p>Moderate changes in the size of the outward (hyperpolarizing) current that is generated directly by the electrogenic Na/K exchange pump in the surface membrane of cardiac Purkinje fibers can cause substantial alterations in the shape of the action potential, in the level of the diastolic potential, or of the resting potential of quiescent cells, or in the rate of firing of spontaneously active preparations. Transient increments in Na/K pump current, of suitable magnitude, can be elicited experimentally in small canine Purkinje fibers by causing a transient increase in their intracellular Na concentration, [Na]i, and, thereby, a transient increase in the rate of electrogenic Na extrusion. Two techniques were used to increase [Na]i: in the first, the rate of Na extrusion from the cells was temporarily reduced by omitting K ions from the bathing fluid for short periods of time, in the second, the rate of Na entry into the cells was temporarily increased by electrically stimulating the preparations rapidly (e.g., greater than or equal to 2 Hz) for brief periods. After the extracellular K concentration was restored, or after electrical stimulation was stopped, respectively, use of a two-microelectrode voltage-clamp technique allowed the resulting increments in pump current to be measured directly, as changes in holding current. Increments in pump current elicited by these two methods in the same preparation decline with the same exponential time-course. In preparations stimulated electrically at a regular, low rate (e.g., less than or equal to 1 Hz) both methods of temporarily stimulating the Na/K pump cause a marked, transient reduction in the duration of the action potential. A closely similar reduction in action-potential duration to that observed during enhanced pump activity can be elicited by injecting, from an external source, a steady hyperpolarizing current of magnitude similar to that of the increment in pump current recorded in the same preparation under voltage clamp.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13722072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1985-01-01DOI: 10.1007/978-1-4757-1287-2_15
C Guarnieri, C Muscari, C M Caldarera
Cyanide-resistant respiration in heart homogenates supplemented with 1 mM NADH was greater in hypertrophied homogenates (60 days banding) with respect to control homogenates, particularly when the homogenates were incubated in 100% oxygen. The intermyofibrillar mitochondria from hypertrophied hearts produced more superoxide radicals than sub-sarcolemmal mitochondria, and both values were greater than in the unbanded group. H2O2 formation was more evident in the intact mitochondria prepared from hypertrophied hearts than in those of the control hearts. Moreover, the perfusion of isolated hearts in anoxic and reoxygenated conditions caused a greater lipoperoxidative and functional damage at the mitochondrial level in hypertrophied hearts than in the control hearts. These results, correlate with the reduction in mitochondrial function found in the overloaded hearts, suggest an involvement of the reactive species of oxygen in the formation of cardiac damage induced by prolonged aortic banding.
在心脏匀浆中添加1 mM NADH的匀浆(带60天)中,与对照匀浆相比,增厚匀浆(带60天)的抗氰呼吸作用更大,特别是当匀浆在100%氧气中孵育时。肥大心脏的肌纤维间线粒体比肌下线粒体产生更多的超氧自由基,两者均大于非带状组。在肥大心脏制备的完整线粒体中,H2O2的形成比对照心脏更明显。此外,在缺氧和再氧条件下灌注离体心脏,肥大心脏在线粒体水平上的脂质氧化和功能损伤大于对照心脏。这些结果与在超载心脏中发现的线粒体功能减少有关,表明活性氧参与了主动脉带带延长引起的心脏损伤的形成。
{"title":"Oxygen radicals and tissue damage in heart hypertrophy.","authors":"C Guarnieri, C Muscari, C M Caldarera","doi":"10.1007/978-1-4757-1287-2_15","DOIUrl":"https://doi.org/10.1007/978-1-4757-1287-2_15","url":null,"abstract":"<p><p>Cyanide-resistant respiration in heart homogenates supplemented with 1 mM NADH was greater in hypertrophied homogenates (60 days banding) with respect to control homogenates, particularly when the homogenates were incubated in 100% oxygen. The intermyofibrillar mitochondria from hypertrophied hearts produced more superoxide radicals than sub-sarcolemmal mitochondria, and both values were greater than in the unbanded group. H2O2 formation was more evident in the intact mitochondria prepared from hypertrophied hearts than in those of the control hearts. Moreover, the perfusion of isolated hearts in anoxic and reoxygenated conditions caused a greater lipoperoxidative and functional damage at the mitochondrial level in hypertrophied hearts than in the control hearts. These results, correlate with the reduction in mitochondrial function found in the overloaded hearts, suggest an involvement of the reactive species of oxygen in the formation of cardiac damage induced by prolonged aortic banding.</p>","PeriodicalId":77831,"journal":{"name":"Advances in myocardiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1985-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14116923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}