正常家鸽的宽频带心电图时域值和功率谱

实验用南京新博公司生产的NHE-1000型宽频带心电信息检测分析仪,研究了正常家鸽宽频带心电图(WFB-ECG)的时域值和QRS波群的功率谱。主要结果如下:(1)Ⅱ、Ⅲ、aVF导联,QRS波群均为主波向下,形成rS或 rSr’型,无Q波,与人类相应导联的心电图波形相反;S波的升支均有一较大的切迹(无一例外),Ⅱ导联切迹幅度为 0.413±0.133mV,宽度为9.733±1.291ms;Ⅱ、Ⅲ、aVF导联T波直立,方向均与主波相反门(1例除外)。aVR导联,QRS波群主波向上,形成Rs型,T波倒置,与主波方向相反(无一例外),也与人类aVR导联的波形相反。(2)P波时程与P-R段之比值为0.8,而人的为1.0-1.6,小鼠的为0.4。(3)Ⅱ导联QRS波群的功率谱特点:以低频信号(低于80 HZ)为主,而高频频段的相对能量比小鼠的低,比人的高,其中高频频段100-1000 Hz的相对能量为(10.181±7.443)％,80-300HZ为(15.418±10.579)％。(4)QRS波群的额面心电轴为-118°±10°(-96°～-136°);(5)心电向量环的位置与人类的相反,位于-90°～-180°相限。这些现象的产生原因可能是由于家鸽心室 Purkinje纤维末梢延伸到心外膜下心肌,导致心外膜下心肌先除极化,心内膜下心肌后除极化而产生的。     

The electrocardiogram of Macaca fascicularis

Electrocardiograms from 16 male cynomolgus monkeys (Macaca fascicularis) were studied. Standard and augmented limb leads (I, II, III, aVR, aVL, aVF) were obtained with the animals restrained in a sitting position. Normal electrocardiographic parameters were determined, including PR and QT intervals; P, QRS, and T wave axes; P and QRS wave widths. Voltages in all standard and augmented limb leads were lower than previously reported for similar size monkeys.     

兔心室肌细胞电生理异质性研究--缺血对动作电位和钾流的影响

实验用全细胞膜片箝技术,观察正常及缺血条件下,兔心内膜下心室肌细胞与心外膜下心室肌细胞的动作电位和稳态外向钾流及其变化。结果显示：（１）正常条件下,心外膜下心室肌细胞与心内膜下心室肌细胞动作电位形态有差异,心外膜下心室肌细胞动作电位时程（ＡＰＤ）较短,复极１期后有明显的初迹,动作电位形态是“锋和圆顶”,而心内膜下心室肌细胞ＡＰＤ较长,并且没有上述动作电位形态特征。这两类细胞静息电位无差异。（２）在     

压力负荷性心衰小鼠左心室跨壁L-型钙电流的变化

为了观察正常和心衰时心内膜下和心外膜下心肌细胞L-型钙电流(ICa-L)的差别,我们采用主动脉弓狭窄的方法建立小鼠压力超负荷性心衰模型,采用全细胞膜片钳技术记录了正常、主动脉狭窄(band)及假手术对照(sham)组动物左心室游离壁内、外膜下心肌细胞的动作电位时程(action potential duration,APD)和ICa-L。结果显示:(1)与sham组同龄的正常小鼠左心室心内膜下细胞动作电位复极达90％的时程(APD90)为(38．2±6．44)ms,较心外膜下细胞的APD90(15.67±5.31)ms明显延长,二者的比值约为2．5:1;内膜下细胞和外膜下细胞ICa-L密度没有差异,峰电流密度分别为(-2.7±0.49)pA/pF和(-2.54±0．53)pA/pF;(2)Band组内、外膜下细胞的动作电位复极达50％的时程(APD50)、APD90均较sham组显著延长,尤以内膜下细胞延长突出,分别较sham组延长了400％和360％,内、外膜下细胞APD90的比值约为4.2:1;(3)与sham组相比, band组内膜下细胞ICa-L密度显著减小,在+10 mV～+40 mV的4个电压下分别降低了20．2％、21．4％、21.6％和25.7％(P< 0．01),但其激活电位、峰电位和翻转电位没有改变;band组外膜下细胞的ICa-L密度与同期sham组相比无明显变化;band组钙通道激活、失活及复活的动力学特征与sham组相比没有改变。以上结果提示,生理状态下小鼠左心室内、外膜下细胞ICa-L密度不存在明显差别,提示ICa-L与APD跨壁异质性的产生无关;心衰时左心室内、外膜下细胞APD明显延长,以内膜下细胞延长尤为突出,内膜下细胞ICa-L密度明显减少,而外膜下细胞ICa-L密度无明显改变,这种ICa-L的非同步变化在心衰时可能起到对抗APD延长、减少复极离散度的有益作用。     

Effect of magnesium sulfate administration on subendocardial and subepicardial perfusion

The objective of this study was to determine the effect of systemic MgSO₄ infusion on subendocardial and subepicardial perfusion. Seventeen spontaneously breathing piglets were examined. Myocardial perfusion was measured using radiolabeled microspheres at baseline, 30 and 60 min after either MgSO₄ (80 mg/kg) or saline infusion. Blood pressure, heart rate, and cardiac output were also measured at these time intervals. Comparison of the magnesiuminduced changes in systemic blood pressure and on subendocardial and subepicardial perfusion at 30 and 60 min with values obtained with saline solution at 30 and 60 min, yielded no statistically significant difference (Tables 1–3). The ratio of subendocardial/subepicardial blood flow and subendocardial and subepicardial coronary vascular resistance at 30 and 60 min revealed no statistically significant differences between the magnesium and the control group (Table 3). There were no statistically significant difference in cardiac output and heart rate during any of the measured periods (Table 2). Our results suggest that the administration of MgSO₄ does not alter the ratio of subendocardial/subepicardial blood flow and the ratio of subendocardial/subepicardial coronary vascular resistance.     

Modeling of IK1 mutations in human left ventricular myocytes and tissue

Elucidation of the cellular basis of arrhythmias in ion channelopathy disorders is complicated by the inherent difficulties in studying human cardiac tissue. Thus we used a computer modeling approach to study the mechanisms of cellular dysfunction induced by mutations in inward rectifier potassium channel (K(ir))2.1 that cause Andersen-Tawil syndrome (ATS). ATS is an autosomal dominant disorder associated with ventricular arrhythmias that uncommonly degenerate into the lethal arrhythmia torsade de pointes. We simulated the cellular and tissue effects of a potent disease-causing mutation D71V K(ir)2.1 with mathematical models of human ventricular myocytes and a bidomain model of transmural conduction. The D71V K(ir)2.1 mutation caused significant action potential duration prolongation in subendocardial, midmyocardial, and subepicardial myocytes but did not significantly increase transmural dispersion of repolarization. Simulations of the D71V mutation at shorter cycle lengths induced stable action potential alternans in midmyocardial, but not subendocardial or subepicardial cells. The action potential alternans was manifested as an abbreviated QRS complex in the transmural ECG, the result of action potential propagation failure in the midmyocardial tissue. In addition, our simulations of D71V mutation recapitulate several key ECG features of ATS, including QT prolongation, T-wave flattening, and QRS widening. Thus our modeling approach faithfully recapitulates several features of ATS and provides a mechanistic explanation for the low frequency of torsade de pointes arrhythmia in ATS.     

Morphological characteristics of tissue components of various layers of the rat myocardium in the early period of development of myocardial hypertrophy]

The tissue components of the subendocardial, intramural and subepicardial layers of the myocardium of rats were examined by morphometry on the 10 day after 50% subphrenic coarctation of the abdominal aorta. The decrease of the relative volume of cardiomyocytes in the subendocardial layer and the increase of this index in the other layers of myocardium were discovered. The decrease of the surface of cardiomyocytes was maximal in the intramural layer and in the other examined layers the decrease was less. Some increase of the average diameters of cardiomyocytes in subepicardial and intramural layers was shown. The cardiomyocytes diameter practically did not change in the subendocardial layer. The increase of the relative volume and surface of the capillaries was revealed in the subendocardial layer. These indexes were decreased in a different degree in the subepicardial and intramural layers.     

Biphasic tissue Doppler waveforms during isovolumic phases are associated with asynchronous deformation of subendocardial and subepicardial layers.

Subendocardial and subepicardial layers of the left ventricle (LV) are characterized with right- and left-handed helical orientations of myocardial fibers. We investigated the origin of biphasic deformations of the LV wall during isovolumic contraction (IVC) and relaxation (IVR). In eight open-chest adult pigs, strain rates were measured along the right- and left-handed helical directions in the LV anterior wall by implanting 16 sonomicrometry crystals. Sonomicrometry strain rates were compared with the longitudinal subendocardial strain rates obtained by tissue Doppler imaging. During ejection and diastolic filling, shortening and lengthening occurred synchronously along the right- and left-handed helical directions. However, during IVC and IVR, the deformations were dissimilar in the two directions. Transmural shortening during IVC occurred along the right-handed helical direction and was accompanied with transient lengthening in the left-handed helical direction. Conversely, during IVR, the LV lengthened along the left-handed helical direction and shortened in the right-handed helical direction. Peak subendocardial strain rates obtained by tissue Doppler imaging during IVC and IVR correlated with corresponding sonomicrometry strain rate values obtained along the right- and left-handed helical directions (r = 0.81, P < 0.001 and r = 0.70, P = 0.001, respectively). Our data suggest that brief counterdirectional movements occur within the LV wall during IVC and IVR. Shortening along the right-handed helical direction is accompanied with reciprocal lengthening in the left-handed helical direction during IVC and vice versa during IVR. The results support an association between asynchronous deformation of subendocardial and subepicardial muscle fibers and the biphasic isovolumic movements observed with high-resolution tissue Doppler imaging.     

Relative Roles of the Ankle and Hip Muscles in Human Postural Control in the Frontal Plane during Standing

The main goal was to evaluate the relative roles of the ankle and hip muscles in human postural control in the frontal plane during normal upright standing. Experiments were designed to compare upright standing with and without the involvement of the ankle joint. The results demonstrated that standing balance in the frontal plane depended largely on the hip muscles and just slightly on the ankle muscles, which performed only small adjusting movements in the frontal plane. During quiet standing, the human body swayed in the frontal plane as a two-component inverted pendulum or, when no ankle joint torque was permitted, as an inverted pendulum consisting of only one component.     

Effect of acidosis on transient outward potassium current in isolated rat ventricular myocytes

The effect of acidosis on the transient outward K(+) current (I(to)) of rat ventricular myocytes has been investigated using the perforated patch-clamp technique. When the holding potential was -80 mV, depolarizing pulses to potentials positive to -20 mV activated I(to) in subepicardial cells but activated little I(to) in subendocardial cells. Exposure to an acid solution (pH 6.5) had no significant effect on I(to) activated from this holding potential in either subepicardial or subendocardial cells. When the holding potential was -40 mV, acidosis significantly increased I(to) at potentials positive to -20 mV in subepicardial cells but had little effect on I(to) in subendocardial cells. The increase in I(to) in subepicardial cells was inhibited by 10 mM 4-aminopyridine. In subepicardial cells, acidosis caused a +8.57-mV shift in the steady-state inactivation curve. It is concluded that in subepicardial rat ventricular myocytes acidosis increases the amplitude of I(to) as a consequence of a depolarizing shift in the voltage dependence of inactivation.     

Stenosis differentially affects subendocardial and subepicardial arterioles in vivo

The presence of a coronary stenosis results primarily in subendocardial ischemia. Apart from the decrease in coronary perfusion pressure, a stenosis also decreases coronary flow pulsations. Applying a coronary perfusion system, we compared the autoregulatory response of subendocardial (n = 10) and subepicardial (n = 12) arterioles (<120 microm) after stepwise decreases in coronary arterial pressure from 100 to 70, 50, and 30 mmHg in vivo in dogs (n = 9). Pressure steps were performed with and without stenosis on the perfusion line. Maximal arteriolar diameter during the cardiac cycle was determined and normalized to its value at 100 mmHg. The initial decrease in diameter during reductions in pressure was significantly larger at the subendocardium. Diameters of subendocardial and subepicardial arterioles were similar 10--15 s after the decrease in pressure without stenosis. However, stenosis decreased the dilatory response of the subendocardial arterioles significantly. This decreased dilatory response was also evidenced by a lower coronary inflow at similar average pressure in the presence of a stenosis. Inhibition of nitric oxide production with N(G)-monomethyl-L-arginine abrogated the effect of the stenosis on flow. We conclude that the decrease in pressure caused by a stenosis in vivo results in a larger decrease in diameter of the subendocardial arterioles than in the subepicardial arterioles, and furthermore stenosis selectively decreases the dilatory response of subendocardial arterioles. These two findings expand our understanding of subendocardial vulnerability to ischemia.     

Intramyocardial pressure and coronary extravascular resistance

Intramyocardial pressure is an indicator of coronary extravascular resistance. During systole, pressure in the subendocardium exceeds left ventricular intracavitary pressure; whereas pressure in the subepicardium is lower than left ventricular intracavitary pressure. Conversely, during diastole, subepicardial pressure exceeds both subendocardial pressure and left ventricular pressure. These observations suggest that coronary flow during systole is possible only in the subepicardial layers. During diastolic, however, a greater driving pressure is available for perfusion of the subendocardial layers relative to the subepicardial layers. On this basis, measurements of intramyocardial pressure contribute to an understanding of the mechanisms of regulation of the phasic and transmural distribution of coronary blow flow.     

Subendocardial and subepicardial pressure-flow relations in the rat heart in diastolic and systolic arrest

Ischemic heart disease is more apparent in the subendocardial than in subepicardial layers. We investigated coronary pressure-flow relations in layers of the isolated rat left ventricle, using 15 microm microspheres during diastolic and systolic arrest in the vasodilated coronary circulation. A special cannula allowed for selective determination of left main stem pressure-flow relations. Arterio-venous shunt flow was derived from microspheres in the venous effluent. We quantitatively investigated the pressure-flow relations in diastolic arrest (n=8), systolic arrest at normal contractility (n=8) and low contractility (n=6). In all three groups normal and large ventricular volume was studied. In diastolic arrest, at a perfusion pressure of 90 mmHg, subendocardial flow is larger than subepicardial flow, i.e., the endo/epi ratio is approximately 1.2. In systolic arrest the endo/epi ratio is approximately 0.3, and subendocardial flow and subepicardial flow are approximately 12% and approximately 55% of their values during diastolic arrest. The endo/epi ratio in diastolic arrest decreases with increasing perfusion pressure, while in systole the ratio increases. The slope of the pressure-flow relations, i.e., inverse of resistance, changes by a factor of approximately 5.3 in the subendocardium and by a factor approximately 2.2 in the subepicardium from diastole to systole. Lowering contractility affects subendocardial flow more than subepicardial flow, but both contractility and ventricular volume changes have only a limited effect on both subendocardial and subepicardial flow. The resistance (inverse of slope) of the total left main stem pressure-flow relation changes by a factor of approximately 3.4 from diastolic to systolic arrest. The zero-flow pressure increases from diastole to systole. Thus, coronary perfusion flow in diastolic arrest is larger than systolic arrest, with the largest difference in the subendocardium, as a result of layer dependent increases in vascular resistance and intercept pressure. Shunt flow is larger in diastolic than in systolic arrest, and increases with perfusion pressure. We conclude that changes in contractility and ventricular volume have a smaller effect on pressure-flow relations than diastolic-systolic differences. A synthesis of models accounting for the effect of cardiac contraction on perfusion is suggested.     

Decreased Ca2+ extrusion via Na+/Ca2+ exchange in epicardial left ventricular myocytes during compensated hypertrophy

Hypertension-induced cardiac hypertrophy alters the amplitude and time course of the systolic Ca2+ transient of subepicardial and subendocardial ventricular myocytes. The present study was designed to elucidate the mechanisms underlying these changes. Myocytes were isolated from the left ventricular subepicardium and subendocardium of 20-wk-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY; control). We monitored intracellular Ca2+ using fluo 3 or fura 2; caffeine (20 mmol/l) was used to release Ca2+ from the sarcoplasmic reticulum (SR), and Ni2+ (10 mM) was used to inhibit Na+/Ca2+ exchange (NCX) function. SHR myocytes were significantly larger than those from WKY hearts, consistent with cellular hypertrophy. Subepicardial myocytes from SHR hearts showed larger Ca2+ transient amplitude and SR Ca2+ content and less Ca2+ extrusion via NCX compared with subepicardial WKY myocytes. These parameters did not change in subendocardial myocytes. The time course of decline of the Ca2+ transient was the same in all groups of cells, but its time to peak was shorter in subepicardial cells than in subendocardial cells in WKY and SHR and was slightly prolonged in subendocardial SHR cells compared with WKY subendocardial myocytes. It is concluded that the major change in Ca2+ cycling during compensated hypertrophy in SHR is a decrease in NCX activity in subepicardial cells; this increases SR Ca2+ content and hence Ca2+ transient amplitude, thus helping to maintain the strength of contraction in the face of an increased afterload.     

Electrocardiographic monitoring in the Göttingen minipig

The purpose of the study reported here was to determine conditions for electrocardiographic monitoring in the G?ttingen minipig in view of its use as a second non-rodent species in toxicology studies. Electrocardiograms were recorded from conscious minipigs (6/sex) maintained in a sling. The three standard bipolar limb leads (I, II, III), the three augmented unipolar limb leads (aVR, aVL, aVF), the triangular Nehb-Sp?ri leads (dorsal, axial, ventral) and their corresponding unipolar leads were recorded, and automated analysis of amplitudes and intervals was made. Major QRS patterns were not observed for any of the bipolar and unipolar leads. For triangular leads, the amplitude of waves was higher than that for limb leads, and the rS pattern dominated for dorsal, axial ventral and aV(F)-Ventral leads. The qR pattern dominated in the aV(R)-dorsal lead, whereas consistency and dominant patterns were not observed for the aV(L)-axial lead. For limb leads, the position of the electrode affected the ECG. Electrodes placed on the cubital and stifle joints were the preferred positions since the P- and R-waves were clearly identifiable with amplitudes > 0.2 mV. Also, the T-wave amplitude was (positive or negative) > 0.2 mV in at least two leads, making the determination of the QT-interval accurate. For the triangular leads, the position of the electrode had less influence on the amplitude of deflections. However, if the axial lead is to be used for calculation of intervals and amplitudes, the xyphoid process is the preferred position. In conclusion, the triangular lead system is recommended for recording ECGs in minipigs. Limb leads could be used in connection. The cubital and stifle joints for standard limb leads and the neck, sacrum, and xyphoid process for triangular leads are the preferred positions for electrodes.     

Ischemia-induced changes in sarcolemmal (Na+, K+)-ATPase, K+-pNPPase, sialic acid, and phospholipid in the dog and effects of the nisoldipine and chlorpromazine treatment

This work was undertaken to study functional and structural changes of the cardiac sarcolemmal membrane which was isolated from the ischemic lesion in the dog. The sarcolemmal fraction was prepared, by adopting the method devised by Reeves and Sutko , from the right ventricle and the subendocardial and subepicardial layers of the left ventricle. Ischemic lesion was produced by occlusion of a branch of the left anterior descending coronary artery for a period of 1.5 hr in the thoracotomized dog, followed by release of the occlusion for 3 hr. Nisoldipine, 5 micrograms/kg, was given twice intravenously, and chlorpromazine was infused at a rate of 10 micrograms/kg X min, in addition to the administration of twice bolus doses of 400 micrograms/kg each. Nisoldipine significantly decreased the incidence of premature ventricular contractions and microvascular hemorrhage. Sarcolemmal purity was monitored by using enzyme and chemical markers; the results indicated that the membrane preparation was tenfold purified over the homogenate. Although the activities of ouabain-sensitive (Na+, K+)-ATPase and ouabain-sensitive K+-p-nitrophenylphosphatase ( pNPPase ) of the sarcolemmal preparation isolated from the subendocardial layer were similar to those from the subepicardial layer in the nonischemic left ventricle, a significant decrease in these activities was observed only when the sarcolemmal fraction isolated from the subendocardial layer of ischemic area was compared with that from the subendocardial layer of nonischemic area. In contrast, the sialic acid content of the sarcolemma from the ischemic subendocardial layer was significantly increased compared to that of the nonischemic subendocardial layer. No such changes occurred in sarcolemma prepared from the ischemic subepicardial layer. The total phospholipid content as well as phosphatidylcholine and -ethanolamine contents of the sarcolemmal membrane prepared from the subendocardial layer of ischemic area were significantly decreased compared to nonischemic area. Nisoldipine prevented the ischemia-induced alterations in sarcolemmal (Na+, K+)-ATPase, pNPPase , sialic acid and phospholipids of the subendocardial layer. Chlorpromazine showed a less consistent effect than did Nisoldipine under our experimental conditions. Our study thus demonstrates that the lipid component and function of cardiac sarcolemmal membrane are altered in the early ischemic lesion and that these alterations are nonuniform in distribution and are alleviated by some pharmacological intervention.     

Neck posture and muscle activity are different when upside down: A human volunteer study

Rollover crashes are dynamic and complex events in which head impacts with the roof can cause catastrophic neck injuries. Ex vivo and computational models are valuable in understanding, and ultimately preventing, these injuries. Although neck posture and muscle activity influence the resulting injury, there is currently no in vivo data describing these parameters immediately prior to a head-first impact. The specific objectives of this study were to determine the in vivo neck vertebral alignment and muscle activation levels when upside down, a condition that occurs during a rollover. Eleven human subjects (6F, 5M) were tested while seated upright and inverted in a custom-built apparatus. Vertebral alignment was measured using fluoroscopy and muscle activity was recorded using surface and indwelling electrodes in eight superficial and deep neck muscles. In vivo vertebral alignment and muscle activation levels differed between the upright and inverted conditions. When inverted and relaxed, the neck was more lordotic, C1 was aligned posterior to C7, the Frankfort plane was extended, and the activity of six muscles increased compared to upright and relaxed. When inverted subjects were asked to look forward to eliminate head extension, flexor muscle activity increased, C7 was more flexed, and C1 was aligned anterior to C7 versus upright and relaxed. Combined with the large inter-subject variability observed, these findings indicate that cadaveric or computational models designed to study injuries and prevention devices while inverted need to consider a variety of postures and muscle conditions to be relevant to the in vivo situation.     

Postural response characterization of standing humans to multi-directional,predictable and unpredictable perturbations to the arm

When the arm of a standing human is perturbed in an unpredictable direction, postural muscles are activated at latencies as short as 50–110 ms. While the motion of the body clearly progresses in hand-to-leg sequence, there is no systematic muscle activation sequence from the arm to the leg muscles, suggesting that the activation of the muscles is not likely the result of local stretch reflexes. In fact, the lower limb muscles are activated before the upright posture is significantly disturbed. The short-latency activation amplitude and the activation probability are clearly tuned to the direction of the arm perturbation for both rostral and caudal muscles. The effect of central set on the short-latency response has been investigated by manipulating the predictability of the perturbations. Possible underlying neural mechanisms have been discussed.