Contrast effects of isoproterenol and ouabain on left ventricular diastolic relaxation dysfunction in isolated, blood-perfused rabbit hearts

We studied the influence of inotropic agents on prompt and transient left ventricular (LV) diastolic relaxation dysfunction produced by superimposition of pacing tachycardia on low-flow ischemia, using an isolated, blood-perfused and isovolumic (balloon-in-LV) rabbit heart preparation. The LV balloon volume was adjusted to produce an LV end-diastolic pressure (EDP) of 15 mmHg and was held constant thereafter. Coronary perfusion pressure was adjusted to 100 mmHg during baseline and to 20 mmHg during low-flow ischemia of 6 min. At baseline, isoproterenol and ouabain were administered to cause moderate and similar rises (14 +/- 3 and 16 +/- 4% above baseline values, respectively) in maximum + dp/dt of LVP with no change in LVEDP. In control hearts which received no drug, superimposition of 5-min pacing tachycardia on low-flow ischemia produced a significant and transient increase in LVEDP under constant LV volume (from 13.4 +/- 0.4 to 24.7 +/- 3.3 mmHg, p less than 0.01). In the hearts which received isoproterenol it did not change LVEDP (from 14.0 +/- 0.4 to 16.2 +/- 1.0 mmHg, NS). In contrast, the ouabain hearts showed a further increase in LVEDP (from 13.7 +/- 0.8 to 29.9 +/- 4.6 mmHg, p less than 0.01). LV developed pressure, myocardial oxygen consumption or myocardial lactate production during pacing tachycardia superimposed on the low-flow ischemia did not differ significantly among the 3 groups. Thus, isoproterenol markedly improved transient LV relaxation dysfunction produced by superimposition of pacing tachycardia on low-flow ischemia, in which an equipotent inotropic dose of ouabain exaggerated the relaxation dysfunction. These results suggest that calcium overload rather than ATP depletion per se contributes to transiently impaired diastolic relaxation by pacing tachycardia and low-flow ischemia.     

Effects of nifedipine on diastolic abnormalities in low-flow and pacing-induced ischemia in isolated rat hearts

An animal experimental model which stimulates human effort angina, especially in terms of diastolic abnormalities, was developed using isovolumically beating perfused rat hearts. Using this model, we studied the effects of nifedipine, a Ca2+ channel blocker, on diastolic properties during pacing-induced ischemia. When the preload of the left ventricle was set at a low level, low-flow ischemia (coronary perfusion pressure of 40 mmHg) plus tachycardia (480 beats/min for 4 min) did not induce an increase in left ventricular end-diastolic pressure (LVEDP). However, with a high preload, low-flow ischemia plus pacing tachycardia induced an increase in LVEDP of 8.4 +/- 5.4 mmHg (p less than 0.01) and a prolongation of the time constant of ventricular pressure decline (6.8 +/- 4.6 msec, p less than 0.05) immediately after pacing tachycardia. Pretreatment with nifedipine (3 x 10(-8) M) prevented the rise in LVEDP induced by pacing tachycardia. Thus, in isolated perfused hearts, diastolic abnormalities similar to those seen in angina pectoris were obtained by low-flow ischemia plus pacing tachycardia. The response to nifedipine suggested that an alteration of Ca2+ movement may play an important role in the increase in left ventricular stiffness under these conditions.     

Acute alterations in diastolic left ventricular chamber distensibility: mechanistic differences between hypoxemia and ischemia in isolated perfused rabbit and rat hearts

Changes in diastolic chamber distensibility (DCD) during hypoxemia and ischemia were studied in isolated-buffer-perfused rabbit hearts. Two minutes of hypoxemia (low PO2 coronary flow) resulted in a shift of the diastolic pressure-volume curve to the left, i.e., distensibility was decreased (hypoxemic contracture). In contrast, 2 minutes of ischemia (zero coronary flow) resulted in an initial shift of the diastolic pressure-volume curve to the right indicating increased distensibility, which was followed by a later (30 minutes) shift to the left (ischemic contracture). Two minutes of ischemia superimposed on hypoxemia caused complete reversal of contracture. A quick stretch and release applied to the myocardium reversed late ischemic contracture but did not effect early hypoxemic contracture. The role of intracellular pH in modulating changes in DCD during hypoxia and ischemia was studied using phosphorus-31 nuclear magnetic resonance spectroscopy of isolated-buffer-perfused rat hearts that demonstrated changes in DCD similar to rabbit hearts during hypoxemia and ischemia. Intracellular pH decreased from 7.03 +/- 0.02 to 6.87 +/- 0.03 (p less than .01) during 2 minutes of ischemia but did not change significantly during 4 minutes of hypoxemia. When 2 minutes of ischemia were superimposed on hypoxemia, pH decreased from 6.99 +/- 0.01 during hypoxemia to 6.88 +/- 0.02 after 2 minutes of ischemia (p less than .01), concomitant with the complete reversal of hypoxemic contracture. These results suggest different mechanisms for late ischemic and early hypoxemic contracture and also suggest an explanation for the opposite initial changes in DCD seen after brief periods of ischemia and hypoxemia. The early development of contracture during hypoxemia and rapid redevelopment of diastolic tension after quick stretching are consistent with the hypothesis that hypoxemic contracture results from persistent Ca++-activated diastolic tension secondary to impaired calcium resequestration by the sarcoplasmic reticulum. In contrast, the late development of contracture during global ischemia and reversal by quick stretching is compatible with rigor bond formation. The initial increase in distensibility during early ischemia and the reversal of hypoxemic contracture by a brief period of superimposed ischemia probably is the result of two factors present during ischemia but not during hypoxemia: the collapse of the coronary vasculature and loss of the "erectile" effect and, the rapid development of intracellular acidosis, which has been shown to affect myofibrillar calcium sensitivity, and this may lead to a decrease in Ca++ activated diastolic tension.     

Acute decrease in left ventricular diastolic chamber distensibility during simulated angina in isolated hearts

It is not clear what factors contribute to the prompt and reversible decrease in left ventricular diastolic chamber distensibility during angina pectoris that is induced by an increase in myocardial energy demand due to exercise or pacing tachycardia. To simulate the demand ischemia that occurs clinically during pacing-induced angina, we used isolated, blood-perfused rabbit hearts with restricted coronary flow and increased myocardial energy demand. A constant left ventricular balloon volume model was used to measure left ventricular diastolic chamber distensibility during 6 minutes of low-flow global ischemia, induced by a reduction in coronary perfusion pressure from 100 to 20 mm Hg. To investigate the influence of different levels of myocardial energy demand, the effects of two different heart rates were studied during low-flow global ischemia; pacing tachycardia (6.4 +/- 0.2 Hz, n = 7) was compared with the rabbit's baseline heart rate of 4 Hz (n = 7). Low-flow ischemia caused a marked decrease in contractile function relative to the baseline preischemic state. In the pacing-tachycardia group, myocardial energy demand, as estimated by the rate X systolic pressure product, was significantly greater than in the constant heart-rate group. When tachycardia was imposed during low-flow global ischemia, there was a transient and reversible increase in isovolumic left ventricular end-diastolic pressure from 14 +/- 1 to 25 +/- 4 mm Hg (measured during long diastoles obtained with transient cessation of pacing) in the pacing-tachycardia group, but there was no increase in left ventricular end-diastolic pressure during low flow ischemia in the constant heart-rate group with lower energy demand (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Heterogeneity of ventricular fibrillation dominant frequency during global ischemia in isolated rabbit hearts

Introduction : Ventricular fibrillation (VF) studies show that ECG‐dominant frequency (DF) decreases as ischemia develops. This study investigates the contribution of the principle ischemic metabolic components to this decline. Methods and Results: Rabbit hearts were Langendorff‐perfused at 40 mL/min with Tyrode's solution and loaded with RH237. Epicardial optical action potentials were recorded with a photodiode array (256 sites, 15 × 15 mm). After 60 seconds of VF (induced by burst pacing), global ischemia was produced by low flow (6 mL/min), or the solution changed to impose hypoxia (95% N₂/5% CO₂), low pH_o (6.7, 80% O₂/20% CO₂), or raised [K⁺]_o (8 mM). DF of the optical signals was determined at each site. Conduction velocity (CV), action potential duration (APD90), effective refractory period (ERP), activation threshold, dV/dt_max, and membrane potential were measured in separate experiments during ventricular pacing. During VF, ischemia decreased DF in the left ventricle (LV) (to [58 ± 6]%, P < 0.001), but not the right (RV) ([93 ± 5]%). Raised [K⁺]_o reproduced this DF pattern (LV: [67 ± 12]%, P < 0.001; RV: [95 ± 9]%). LV DF remained elevated in hypoxia or low pH_o. During ventricular pacing, ischemia decreased CV in LV but not RV. Raised [K⁺]_o did not change CV in either ventricle. Ischemia and raised [K⁺]_o shortened APD90 without altering ERP. LV activation threshold increased in both ischemia and raised [K⁺]_o and was associated with diastolic depolarization and decreased dV/dt_max. Conclusions: These results suggest that during VF, decreased ECG DF in global ischemia is largely due to elevated [K⁺]_o affecting the activation thresholds in the LV rather than RV.     

大豆磷脂对缺血再灌注家兔左室功能的影响

本文报道缺血再灌注时家兔左室功能的变化及大豆磷脂对它的影响。结果显示:结扎冠脉左室支中点４５ｍｉｎ、再灌注１８０ｍｉｎ时，左室收缩功能和舒张顺应性呈渐进性降低。在结扎前和再灌注即刻以脂质体形式补充大豆磷脂可减轻左室收缩和舒张功能的降低，并可降低血浆乳酸脱氢酶活性。提示:大豆磷脂对缺血再灌注时家兔左室功能的损伤具有保护作用。     

Comparative effects of hypoxia and ischemia in the isolated, blood-perfused dog heart: evaluation of left ventricular diastolic chamber distensibility and wall thickness

To compare the effects of hypoxia and ischemia on left ventricular (LV) diastolic function, we studied 17 isolated, isovolumic dog hearts by measuring LV diastolic chamber distensibility (LV end diastolic pressure at constant volume), wall thickness, and myocardial pH in response to hypoxia at constant coronary flow or pressure versus global ischemia (zero coronary blood flow). Hypoxic perfusates consisted of methemoglobin-containing red blood cells suspended in lactated Ringer's solution. Brief cross-clamping of the coronary perfusion line was used to assess the contribution of coronary turgor to chamber distensibility and wall thickness. With hypoxia, left ventricles showed a significant early (5 minutes) decrease in diastolic distensibility and an increase in wall thickness, at either constant coronary perfusion pressure or flow. The increase in wall thickness was independent of hypoxia-induced changes in coronary turgor. In contrast, global ischemia produced an early increase in LV diastolic chamber distensibility and a decrease in wall thickness. When global ischemia was continued beyond 60 minutes, a decrease in LV chamber distensibility developed. This diastolic contracture was not associated with an increase in LV wall thickness. Myocardial pH decreased slightly during 15 minutes of hypoxia and markedly with 15 minutes of global ischemia. Thus, LV diastolic chamber distensibility decreased during 15 minutes of hypoxia, while an increase in distensibility was seen during global ischemia of similar duration. During hypoxia, these changes were associated with increased LV wall thickness, at either constant coronary perfusion pressure or constant coronary flow. Prolonged ischemia led to diastolic contracture without an increase in wall thickness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ischemia on myocardial function during rapid left ventricular pacing

INTRODUCTION: Coronary artery disease is often accompanied with deterioration in left ventricular function. Left ventricular pacing has been shown to improve cardiac function in chronic heart failure. However, data are limited about left ventricular pacing during acute ischemia. Therefore, we studied the effects of acute myocardial ischemia on myocardial function during left ventricular pacing. METHODS: In 8 anesthetized dogs, the left ventricle was rapidly paced (180 bpm) from a basolateral and apicoseptal site during normal perfusion and mild and severe ischemia of the left anterior descending coronary artery. Effects on myocardial function were measured at each level of ischemia before and during pacing. RESULTS: Significant differences (p < 0.05) between basolateral and apicoseptal pacing were found for segmental shortening (12.1+/-1.6 vs. 10.8+/-1.6%), and QRS duration (77.3+/-4.1 vs. 85.7+/-3.8 ms) at normal coronary perfusion. During mild ischemia, significant differences (p < 0.05) were seen for myocardial contractility dP/dt(max) (1277+/-197 vs. 1158+/-156 mm Hg/s), segmental shortening (10.3+/-1.9 vs. 8.1+/-1.7%), left ventricular end-systolic pressure (76.9+/-7.5 vs. 69.6+/-7.9 mm Hg), and QRS duration, and for myocardial contractility dP/dt(max) (1033+/-209 vs. 917+/-207 mm Hg/s) and left ventricular end-systolic pressure (69.2+/-13.5 vs. 62.2+/-15.0 mm Hg) during severe ischemia. There were no significant differences in coronary blood flow during pacing from both sites. CONCLUSIONS: During acute myocardial ischemia, depression of left ventricular function was lowest, when pacing from a left ventricular basolateral site. The effects of rapid left ventricular pacing were amplified by reduced coronary perfusion pressures. The choice of pacing site did not relevantly influence coronary blood flow.     

Ionic and electrical effects of ouabain on isolated rabbit hearts

The effects of ouabain (0.5 × 10^?6m) on the intracellular ionic concentrations and the transmembrane potential were studied. Isolated rabbit hearts were perfused at 33°C and constant coronary flow. Krebs solution containing [¹⁴C]inulin was used to measure the extracellular space (ECS). The cell Na and K content were determined after 10 and 60 min perfusion with ouabain. The membrane potential was measured throughout the experiment. Ouabain produced a decrease in ECS and cell potassium ([K]_i) and an increase in intracellular sodium ([Na]_i) and water. There was a time lag between the change in [Na]_i and the change in [K]_i. A positive inotropic effect occurred during the first 10 to 20 min of perfusion with ouabain. The resting potential (RP) and action potential amplitude (APA) decreased with a similar time course, reaching values of 63 and 55% of the control by the end of the 60 min period. The maximum rate of depolarization ($\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$) decreased after 10 min, levelling off at about 50% of the control at 30 min. An early lengthening of the plateau was followed by progressive shortening of the action potential. It is postulated that the depolarization is due to inhibition of an electrogenic ionic pump, that the changes in APA are due to ionic shifts and depolarization, and that the values of $\text{V}\text{?}{}_{\mathrm{<mtext>max</mtext>}}$ are largely determined by shifts in the h_∞ curve.     

Ventricular fibrillation during no-flow global ischemia in isolated rabbit hearts

Introduction: The dominant frequency (DF) during ventricular fibrillation (VF) in Langendorff-perfused guinea pig hearts is higher in left ventricle (LV) than in right ventricle (RV). However, the onset of VF invariably leads to global ischemia. Whether or not a high DF source exists in LV during global ischemia is unknown.
Methods and Results: By using a two-camera optical mapping system, epicardial activation patterns of VF were studied in 12 isolated rabbit hearts during baseline, no-flow global ischemia, and reperfusion. Simultaneous endocardial electrode recording was performed in 4 of the 12 hearts. Optical mapping showed type 1 VF at baseline, with multiple wandering and short-lived wavelets. After the onset of global ischemia, VF showed progressively increased spatiotemporal periodicity. The majority (65%) of VF recorded after 7 minutes of global ischemia showed type 2 VF, containing a single epicardial site with stable (≥3.85 seconds in duration) repetitive activities. Among the 33 sites with these activities, 24 were located near the interventricular septum, and 27 showed an epicardial breakthrough pattern with centrifugal propagation and wavebreaks distant from the focal site. After 10 minutes of global ischemia, the DF was lower on LV epicardium (5.0 ± 1.4 Hz) than on RV epicardium (8.6 ± 2.5 Hz, P < 0.001). However, there was no DF gradient between RV and LV endocardium (9.7 ± 1.0 vs 9.6 ± 0.9 Hz).
Conclusions: VF during prolonged global ischemia is consistent with type 2 VF with a single subepicardial source of rapid activation, mostly near the interventricular septum. The DF in LV is not higher than in RV.     

Early recurrence of ventricular fibrillation after successful defibrillation during prolonged global ischemia in isolated rabbit hearts

Introduction: The mechanisms that lower the efficacy of electrical defibrillation during prolonged global ischemia remain unclear.
Methods and Results : Epicardial activation patterns during attempted electrical defibrillation were studied in 18 Langendorff-perfused rabbit hearts at baseline, after 5-minute no-flow global ischemia and after 10-minute reperfusion. DFT₅₀ (voltage required to achieve 50% probability of successful defibrillation) was determined at each stage. Defibrillation was considered successful if postshock sinus/idioventricular rhythm was present. Prolonged global ischemia converted type 1 VF (multiple wandering wavelets) into type 2 VF (repetitive epicardial breakthroughs, REBs). The mean DFT₅₀ after 5-minute ischemia (96 ± 39 V) was significantly lower when compared with that at baseline (154 ± 47 V, P < 0.0001) and after 10-minute reperfusion (145 ± 47 V, P < 0.001). However, the incidence of early (within 10 seconds) VF recurrence after successful shock during prolonged global ischemia (23 of 78, 29.5%) was much higher than that at baseline (2 of 60, 3.3%) and after 10-minute reperfusion (5 of 63, 7.9%; P < 0.0001). Mapping data showed that the VF wavefronts during prolonged global ischemia were initially halted by the shock, followed by one to five ventricular escape beats. These beats then triggered REBs and early VF recurrence. In eight out of 11 episodes, the REBs before and after successful shock arose from the same location near the interventricular septum.
Conclusions : There is a significant reduction of DFT₅₀ during prolonged global ischemia. However, defibrillation appears to fail when the preexisting REBs near the interventricular septum induce early VF recurrence. Shock per se cannot eliminate the substrates of these REBs.     

Effect of dilazep on myocardial contractility following acute ischemia and reperfusion in isolated blood-perfused canine left ventricular muscle

Myocardial protection by dilazep HCl, an antianginal drug and a potent calcium antagonist, against myocardial damage following acute ischemia and reperfusion was studied with respect to myocardial contractility in isolated blood-perfused canine left ventricular muscle. Myocardial function was expressed by percent recovery rate of maximal net developed tension. 1) The coronary infusion of dilazep revealed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. 2) The intravenous administration of dilazep to the support dog and Young's infusion also showed significant myocardial protection during normothermic ischemic arrest of 45 min and reperfusion. Dilazep showed no persistent depression of myocardial contractility due to its calcium antagonistic effect during reperfusion. 3) The combination of intravenous administration of dilazep to the support dog, Young's infusion, and hypothermia showed significant myocardial protection during prolonged ischemia and reperfusion even in hypertrophied ventricle. These results demonstrate that dilazep provides effective myocardial protection during ischemic arrest and reperfusion by preventing abnormal calcium accumulation in myocardial cells during reperfusion. No persistent depression of myocardial contractility during reperfusion may support dilazep's clinical application as a myocardial protective agent in open-heart surgery.     

Effects of respiration on left ventricular diastolic function in healthy children

Pulsed Doppler echocardiographic indices of mitral valve fillingwere measured in 20 healthy children, between 3 and 125 yearsold, in order to evaluate the effects of spontaneous respirationon left ventricular diastolic filling patterns. There were significantrespiratory variations in four parameters of left ventriculardiastolic function: The peak early filling velocity, the ratioof early to late peak filling velocity, and the ratio of earlyto late diastolic velocity-time integral decreased significantlyduring inspiration (mean decrease 7%, P<0·05; 16%,P<0·01; and 12%, P<0·05, respectively).On the other hand there was a significant increase in late peakfilling velocity with inspiration (10% increase, P<0·05).Other variables of left ventricular diastolic filling were unchangedwith inspiration. These results suggest that assessment of leftventricular diastolic function in children should be standardizedwith regard to respiratory phases in any clinical application. (Eur Heart J 1996; 17: 453%456)     

Changes of left ventricular diastolic function in exercising dogs without and with ischemia

Left ventricular (LV) diastolic function in the absence and presence of regional ischemia was examined in eight conscious dogs chronically instrumented with ultrasonic devices for measuring LV wall thickness and volume. During treadmill exercise, ischemia was induced (hydraulic occluder) to produce less than 10% systolic wall thickening in the ischemic zone. LV filling was assessed by the peak filling rate (PFR), mean filling rates in the first and second halves of filling (mFR1 and mFR2), an early filling index from mitral valve opening to minimal diastolic pressure (PDm), and the percentage of atrial filling. Also, LV relaxation (tau) and wall thinning rates during isovolumetric relaxation and the first and second halves of the filling phase were assessed. During control exercise without ischemia, PDm decreased by 2.61 mm Hg (p less than 0.05) to -1.1 mm Hg and there was a downward shift of the entire LV diastolic pressure-volume (P-V) curve. The LV relaxation rate, PFR, mFR1, and mFR2 were enhanced. Early filling was increased by 116%, the percentage of atrial filling by 118%, and overall diastolic filling by 23% despite a 63% decrease in the filling period. During ischemic exercise, systolic function was depressed compared with the resting state, PDm increased by 4.84 mm Hg (p less than 0.005) associated with a pronounced rightward and upward shift of the early portion of the P-V curve. LV relaxation rate, PFR, and mFR1 were reduced, the early filling index fell sharply by 62% but percentage of atrial filling was unchanged, while overall diastolic filling decreased by 30%. The thinning rate of the control wall was enhanced, whereas that of ischemic wall was depressed. Multiple factors contributed to the markedly impaired early and overall diastolic LV filling during ischemia, including impaired systolic function, reduced relaxation rate, nonuniformity of wall motion, an upward shift of the early diastolic P-V curve, and absence of a compensatory increase in late diastolic filling.     

Effects of carvedilol on left ventricular function, mass, and scintigraphic findings in isolated left ventricular non-compaction

A four month old infant with isolated left ventricular non-compaction was treated with carvedilol. Haemodynamic studies and various types of imaging—including echocardiography, radiographic angiography, magnetic resonance imaging, and single photon emission computed tomography with ²⁰¹Tl, ¹²³I-β-methyliodophenylpentadecanoic acid (BMIPP), and ¹²³I-metaiodobenzylguanidine (MIBG)—were performed before and 14 months after treatment. Left ventricular ejection fraction increased from 30% to 57%, and left ventricular end diastolic volume, end systolic volume, and end diastolic pressure showed striking reductions during treatment. Left ventricular mass decreased to about two thirds of the baseline value after treatment. Per cent wall thickening increased after carvedilol in the segments corresponding to non-compacted myocardium. A mismatch between ²⁰¹Tl and BMIPP uptake in the area of non-compaction observed before carvedilol disappeared after treatment. Impaired sympathetic neuronal function shown by MIBG recovered after treatment. Thus carvedilol had beneficial effects on left ventricular function, hypertrophy, and both metabolic and adrenergic abnormalities in isolated left ventricular non-compaction.


Keywords: isolated left ventricular non-compaction; carvedilol; cardiac sympathetic nerve; ventricular remodelling     

Effects of lidocaine on isolated, blood-perfused ventricular contractility in the dog

Direct inotropic effects of lidocaine on ventricular muscle were investigated in isolated canine left ventricular preparations which were perfused with a donor dog's arterial blood. Intravenous administration of lidocaine in doses of less than 1 mg/kg did not cause any significant hemodynamic or cardiac changes in the donor dog and in the isolated ventricular preparation. A large dose of 10mg/kg of lidocaine produced a marked depressor response in the donor and a negative inotropic effect in the isolated ventricle. Direct injection of lidocaine (1-30 micromol) to the isolated preparation induced a dose-related decrease in the ventricular contractile force. Infusion of lidocaine (3 micromol/ml per min) did not influence norepinephrine- or calcium chloride-induced positive inotropic effects. In the frequency-force relationship, lidocaine generally depressed the contractility, exhibiting the positive staircase phenomenon. On the other hand, a calcium entry inhibitor, diltiazem, readily caused the negative staircase. From these results, it is concluded that (1) a large amount of lidocaine has a cardiac depressant property, (2) lidocaine has no antiadrenergic properties, and (3) the action of lidocaine may probably be due to the effect of intracellular calcium movement but not to a modification of Ca inward currents.     

长期血浆内皮素-1水平升高对异丙肾上腺素慢性致室性心律失常作用的影响

目的探讨长期血浆内皮素-1（ET-1）水平升高对异丙肾上腺素（ISO）慢性致室性心律失常（VA）作用的影响。方法雄性新西兰大耳兔60只,采用随机数字法分为对照组、血浆ET-1升高组（ET-1组）、ISO组及ET-1±ISO组,每组15只。所有动物连续14d经耳缘静脉注射药物,对照组注射0.9％NaCl（1ml·kg^-1·d^-1）,ET-1组注射ET-1（10μg·kg^-1·d^-1）、ISO组注射ISO（300μg·kg^-1·d^-1）、ET—I±ISO组同时注射ET-1与ISO（剂量及方法同前）。药物注射7d后,在整体心脏Langendorff灌流条件下行离体电生理研究,分别记录和测量左心室前游离壁（LAF）心外膜单相动作电位（MAP）、有效不应期（VEItP）,并构建动作电位恢复性（APDR）曲线。对所有离体心脏于LAF处,行程控增频电刺激以观察动作电位时限（APD）电交替的发生,猝发快速电刺激用以进行VA的诱发。结果与对照组相比,ISO组90％MAP[MAPD90,（164．91±13．14）ms对（144．13±8．02）ms]、VERP[（144．06±13．73）ms对（129．50±7．65）ms]、APDR曲线最大斜率[Smax,（1．51±0．16）对（0．87±0．12）]、诱发APD电交替的最大起搏周长（PCL）中位数（170ms对130ms）和VA诱发率（86．67％对13．33％）均增大（P均〈0．01）,VERP／MAPD90变化不明显（P〉O．05）。ET-1组MAPD。[（169．41±13．97）ms对（144．13±8．02）ms]、AP—DR曲线Smax[（1．47±0．18）对（0．87±0．12）]、诱发APD电交替的最大PCL中位数（160ms对130ms）及VA诱发率（66．67％对13．33％）均增大（P均〈0．01）,而VERP／MAPD。显著减小[（0．80±0,05）对（0．90±0．04）,P〈O．01],VERP变化不明显（P〉0．05）。ET-1±ISO组各项电生理指标结果与对照组相比均差异无统计学意义（P均〉0．05）;与ISO组相比,ET-1±ISO组MAPD90[（147．66±9．68）ms对（164．91±13．14）ms]、VERP[（130．60±10．75）ms对（144．06±13．73）ms]、APDR曲线Smax[（0．94±0．14）对（1．51±0．16）]、诱发APD电交替的最大PCL中位数（140ms对170ms）及VA诱发率（40．00％对86．67％）均减小（P均〈0．01）,VERP／MAPD。变化不明显（P〉0．05）。结论长期血浆ET-1水平升高可减弱ISO对心脏电生理特性的慢性损害,从而起到抗VA作用。     

Simultaneous assessment of left ventricular systolic and diastolic dysfunction during pacing-induced ischemia

Both systolic and diastolic dysfunction have been described during pacing-induced ischemia, but the temporal sequence of systolic and diastolic impairment has not been established. Accordingly, 22 patients with coronary artery disease were paced at increasing heart rates and studied with simultaneous hemodynamic monitoring, electrocardiographic recording, and radionuclide ventriculography. In addition, with synchronized left ventricular pressure tracings and radionuclide volume curves, three sequential pressure-volume diagrams were constructed for each patient corresponding to baseline, intermediate, and maximum pacing levels. Eleven patients (group I) demonstrated a nonischemic response to pacing tachycardia without chest pain, significant electrocardiographic changes, or significant rise in left ventricular end-diastolic pressure (LVEDP) in the immediate postpacing period. These patients demonstrated a progressive decrease in LVEDP, end-diastolic volume, and end-systolic volume, no change in cardiac output or left ventricular ejection fraction, and a progressive increase in left ventricular diastolic peak filling rate and the end-systolic pressure-volume ratio. Pressure-volume diagrams shifted progressively leftward and slightly downward, suggesting both an increase in contractility and a mild increase in left ventricular distensibility. The remaining 11 patients (group II) exhibited an ischemic response to pacing tachycardia, with each patient experiencing angina pectoris, demonstrating greater than 1 mm ST segment depression on the electrocardiogram, and exhibiting greater than 5 mm Hg rise in LVEDP immediately after pacing. LVEDP, end-diastolic volume, and end-systolic volume in these patients initially decreased and then subsequently increased during angina, with no change in cardiac output but a decrease in ejection fraction. Left ventricular peak diastolic filling rate and the left ventricular end-systolic pressure-volume ratio both increased at the intermediate pacing rate but fell at maximum pacing. Pressure-volume diagrams for these patients shifted leftward initially, then back to the right, during intermediate and peak pacing levels, often with an upward shift in the diastolic pressure-volume relationship. LVEDP in group II was significantly higher than that in group I at the intermediate pacing level with no difference in end-diastolic or end-systolic volumes, suggesting decreased left ventricular distensibility in these patients before the onset of systolic dysfunction at the maximum pacing level.(ABSTRACT TRUNCATED AT 400 WORDS)