Heart Rate Variability in Isolated Rabbit Hearts

The presence of heart rate variability (HRV) in patients with cardiac denervation after heart transplantation raised our interest in HRV of isolated, denervated hearts. Hearts from seven adult white ELCO rabbits were transferred to a perfusion apparatus. All hearts were perfused in the working mode and in the Langendorff mode for 20 minutes each. HRV was analyzed in the frequency domain. A computer simulated test ECG at a constant rate of 2 Hz was used for error estimation of the system. In the isolated, denervated heart, HRV was of random, broadband fluctuations, different from the well-characterized oscillations at specific frequencies in intact animals. Mean NN was 423 ± 51 ms in the Langendorff mode, 406 ± 33 ms in the working heart mode, and 500 ms in the test ECG. Total power was 663 ± 207 ms², 817 ± 318 ms², and 3.7 ms², respectively. There was no significant difference in any measure of HRV between Langendorff and working heart modes. The data provide evidence for the presence of HRV in isolated, denervated rabbit hearts. Left atrial and ventricular filling, i.e., the working heart mode, did not alter HRV, indicating that left atrial or ventricular stretch did not influence the sinus nodal discharge rate.     

"Preconditioning at a Distance" in the Isolated Rabbit Heart

OBJECTIVE: Brief myocardial ischemia evokes a cardioprotective response, referred to as "ischemic preconditioning" (IP), that limits injury caused by a subsequent prolonged ischemic insult. The myocardial IP effect can be induced by ischemia of "distant" cardiac and noncardiac tissue, implicating the involvement of an as-yet-unidentified humoral trigger. If a preconditioning hormone exists, the authors hypothesize that the IP effect should be transferable, via administration of coronary effluent, from a preconditioned donor heart to a virgin non-preconditioned acceptor heart. METHODS: Isolated buffer-perfused rabbit hearts were assigned to one of four treatment groups in a donor/acceptor sequence. Donor hearts underwent either three IP cycles or a matched period of uninterrupted perfusion (control donors). Coronary perfusate collected from IP and control donor hearts was reoxygenated and transfused to virgin acceptor hearts. All hearts then underwent 30 minutes of global ischemia followed by 30 minutes of reperfusion. Left ventricular developed pressure (LVDP) (the authors' index of cardioprotection) was monitored throughout the protocol by a left ventricular (LV) balloon. RESULTS: In donor controls, LVDP assessed at 30 minutes post-reflow was restored to only 49 +/- 5% of baseline values. Recovery of LV function was significantly enhanced in both IP donor hearts (69 +/- 4%*) and IP acceptor hearts (70 +/- 6%*) vs donor controls (*p < 0.05), while, in acceptor controls, intermediate values of LVDP (62 +/- 7%) were obtained. CONCLUSION: The IP effect can be transferred between rabbit hearts, suggesting the presence of a humoral trigger signal for distant preconditioning. Isolating this hormone may have therapeutic and diagnostic implications in the management of acute myocardial ischemia.     

Adrenergic-dependent Effect of Adenosine-induced Ventricular Fibrillation in the Isolated Rabbit Heart

BACKGROUND: The present study examined the contributory role of endogenous catecholamines in adenosine-induced ventricular fibrillation in isolation rabbit hearts. METHODS AND RESULTS: Cardiac catecholamine depletion was induced in eleven rabbits by the administration of 6-hydroxydopamine (2 x 30 mg/kg, every 12 hours intramuscularly). Hearts were removed 24 hours later, and subjected to 12 minutes of hypoxic perfusion followed by 40 minutes of reoxygenation while heart rate was maintained with atrial pacing. One of six, and one of five hearts from 6-hydroxydopamine treated rabbits developed ventricular fibrillation during hypoxia-reoxygenation when exposed to 3,7-dimethyl-1-propargylzanthine (DMPX) (10 μM) + adenosine (ADO) (1 μM) and DMPX (10 μM) + ADO (10 μM), respectively. In hearts from a control group, not exposed to 6-hydroxydopamine, ventricular fibrillation developed in each of five (100% incidence) hearts when perfused in the presence of DMPX (10 μM) + ADO (10 μM) (P <.05). Nadolol (1 μM), a beta-adrenoceptor DMPX (10 μM) + ADO (10 μM) treated hearts (n = 6, P <.05 vs DMPX + ADO treated hearts). To ensure catecholamine depletion, spontaneously beating isolated hearts from vehicle and 6-hydroxydopamine treated rabbits were perfused under normoxic conditions while exposed to increasing concentrations of tyramine (1, 3, 10 mM) and the change in heart rate was determined. A concentration-related, positive chronotorpic response to tyramine was obtained in hearts from the vehicle treated group that was absent in hearts from 6-hydroxy-dopamine treated rabbits or hearts perfused in the presence of nadolol. CONCLUSIONS: The results demonstrate that inhibition of the cardiac adenosine A(2) receptor, unmasks an adenosine A(1) receptor profibrillatory effect that is dependent upon endogenous cardiac catecholamines and beta-adrenoreceptor activation during myocardial hypoxia-reoxygenation.     

自制心脏保存液保存离体兔心的研究

目的：初步探讨自制心脏保存液对离体兔心的保存效果。方法：取18只新西兰白兔，随机成分3组，建立非循环式Langendorff灌注模型，分别用晶体停搏液、uⅣ液和我院自制的心脏保存液在低温下保存4h；复灌后检测左心室压力、心肌酶学指标及心肌含水量。结果：自制心脏保存液组左心室压力、心肌酶学指标及心肌含水量与晶体停搏液组有显著差异，与UW液组无显著差异。结论：实验证实我院自制的心脏保存液与uⅣ液心肌保护效果相近，其配方设计基本可行。     

Are Double Potentials Markers of a Specific Zone of the Atrioventricular Junction in the Isolated Rabbit Heart?

A study is made of the characteristics of the atrial potentials recorded in the Koch triangle and its proximity, their variations on modifying the site of cardiac pacing, and their usefulness as markers of a distinct zone of the AV junction. In 12 isolated and perfused rabbit heart preparations an analysis was made of the endocardial atrial electrograms recorded with a multiple electrode positioned in the AV junction. The electrograms were obtained during spontaneous rhythm and on pacing at the crista terminalis (CT), interatrial septum (IAS), left atrium, and right ventricle. Double potentials were frequently obtained. On pacing at the CT, high-low double potentials (DP [H-L]) were more frequent (P < 0.05) in the low CT (11%± 4% of the electrodes) and posterior zone of the Koch triangle (6%± 5%), than in the IAS (1 %± 2%) and anterior zone of the Koch triangle (2%± 3%). A similar tendency was observed either on pacing at the left atrium or during spontaneous rhythm. During pacing at the IAS the percentages of low-high double potentials (DP[L-H]) were significantly higher (P < 0.05) in the low CT (7%± 6%). DP (H-L) were of low sensitivity in indicating a given zone; maximum sensitivity was 61 % in the low CT when pacing at the CT. DP (L-H) proved even less seusitive in indicating a given zone, though their specificity was greater in the low CT (91%) during pacing at the IAS. The specific zones in which the highest percentages of DP (H-L) or DP (L-H) are obtained depend on the site of cardiac pacing. On pacing at the IAS. DP (L-H) are more specific of the low CT. During pacing at both the CT and at the IAS. DP (H-L) sensitivity in indicating a given zone is low.     

Bile Acid Synthesis in the Isolated, Perfused Rabbit Liver

These experiments were carried out to demonstrate the usefulness of the perfused rabbit liver for studies of bile acid metabolism, and to determine the rate-limiting enzyme of bile acid synthesis. Rabbits were fed a semisynthetic diet, with or without the addition of 1% cholestyramine, under controlled conditions. At the end of 2-5 wk, the livers were removed and perfused for 2.5 hr employing various (14)C-labeled precursors to measure de novo cholic acid synthesis. The livers were then analyzed for cholesterol, and the bile collected during the perfusion was analyzed for cholesterol and bile acids. Control bile contained, on the average, 0.34 mg of glycocholate, 7.4 mg of glycodeoxycholate, and 0.06 mg of cholesterol. After cholestyramine treatment of the donor rabbits, the bile contained 3.3 mg of glycocholate, 3.7 mg of glycodeoxycholate, and 0.05 mg of cholesterol. It was assumed that in cholestyramine-treated animals the enterohepatic circulation of the bile acids had been interrupted sufficiently to release the feedback inhibition of the rate-controlling enzyme of bile acid synthesis. Therefore, a given precursor should be incorporated into bile acids at a more rapid rate in livers of cholestyramine-treated animals, provided that the precursor was acted upon by the rate-controlling enzyme. It was found that the incorporation of acetate-(14)C, mevalonolactone-(14)C, and cholesterol-(14)C into cholate was 5-20 times greater in the livers of cholestyramine-treated animals than in the controls. In contrast, there was no difference in the incorporation of 7alpha-hydroxycholesterol-(14)C into cholate regardless of dietary pretreatment. It was concluded that given an adequate precursor pool, the 7alpha-hydroxylation of cholesterol is the rate-limiting step in bile acid formation.     

Lysophosphatidylcholine and Cellular Potassium Loss in Isolated Rabbit Ventricle

BACKGROUND: Lysophospholipids such as lysophosphatidylcholine (LPC) have many direct electrophysiological effects on cardiac muscle and have been implicated as a cause of lethal ventricular arrhythmias during acute myocardial ischemia. Because extracellular K(+) accumulation is also a key arrhythmogenic factor during acute ischemia, we examined the effects of LPC on cellular K(+) balance, including its interaction with adenosine triphosphate-sensitive K(+) (K(ATP)) channels. METHODS AND RESULTS: Isolated rabbit interventricular septa paced at 75 beats/min were loaded with (42)K(+) to measure unidirectional K(+) efflux rate (in (42)K(+) washout experiments) or tissue K(+) content ((42)K(+) uptake experiments) and action potential duration (APD) during exposure to 20 μM LPC for 30 minutes. LPC caused tissue K(+) content to decrease by 15 +/- 2% (n = 4) at a steady rate over 30 minutes, associated with gradual APD shortening and a delayed increase in unidirectional K(+) efflux rate. Pretreatment with 12 μM cromakalim to selectively activate K(ATP) channels shortened APD by 44 +/- 66% and had no effect on net tissue K(+) content during control aerobic perfusion. However, cromakalim increased net K(+) loss during exposure to LPC to 22 +/- 4%, a 47% increase. CONCLUSIONS: LPC induced net K(+) loss in heart, which was potentiated by the K(ATP) channel agonist cromakalim. This ATP finding suggests that if LPC accumulates to similar levels during myocardial ischemia and hypoxia, it may be an important mechanism in net K(+) loss.     

Delta Opiates Increase Ischemic Tolerance in Isolated Rabbit Jejunum

Mammalian hibernation is mediated by humoral agonists of the delta opioid receptor (DOR). Moreover, transfer of either humoral or synthetic DOR agonists to non-hibernators reportedly induces a state of improved myocardial ischemic tolerance. OBJECTIVE: To determine whether the DOR agonist D-Ala 2, D-Leu 5, enkephalin (DADLE) similarly elicits protection in noncardiac-i.e., mesenteric-tissue. METHODS: In Protocols 1 and 2, the authors developed and characterized an in vitro model of mesenteric ischemia/reperfusion in isolated rabbit jejunum by documenting the effect of increasing ischemic duration (0 to 120 minutes) and the relative importance of glucose and/or oxygen deprivation on the evolution of jejunal injury. In Protocol 3, jejunal segments were randomized to receive either no treatment (controls) or 15 minutes of pretreatment with 1 microM DADLE, followed by 60 minutes of simulated ischemia and 30 minutes of reperfusion. Jejunal injury was quantified by repeated, time-matched assessment of peak contractile force evoked by 1 microM acetylcholine (all protocols) and delineation of tissue necrosis (Protocol 1). RESULTS: Development of significant jejunal injury required combined oxygen/glucose deprivation. Moreover, there was a direct relationship between ischemic duration and tissue injury, and a significant inverse correlation between reperfusion contractile force (% of baseline) and the extent of smooth muscle necrosis (r(2) = 0.87; p < 0.01). Most notably, mesenteric ischemia/reperfusion injury was attenuated by DADLE: reperfusion contractile force was 47 +/- 5% versus 36 +/- 5% in DADLE-treated versus control segments (p < 0.01). CONCLUSIONS: Treatment with the delta opioid agonist DADLE increases ischemic tolerance of isolated rabbit jejunum.     

Isolated Nephron Segments from Rabbit Models of Obstructive Nephropathy

Micropuncture and microcatheterization studies have been used extensively to investigate the pathophysiologic alterations in renal function induced by urinary tract obstruction. The present isolated tubule microperfusion studies were designed to examine the intrinsic alterations in segmental nephron function induced by 24 h of bilateral (BUO) and unilateral (UUO) urinary tract obstruction.Following UUO superficial proximal convoluted tubule reabsorption rate (J(v)) was not different from contralateral control (0.75+/-0.08 vs. 0.73+/-0.11 nl/mm per min, NS). Following UUO J(v) in juxtamedullary proximal convoluted tubules (JMPCT) was reduced 32% (0.69+/-0.06 vs. 0.47+/-0.04 nl/mm per min, P < 0.02). Following UUO J(v) in proximal straight tubules (PST) was reduced 52% (0.25+/-0.02 vs. 0.12+/-0.03, P < 0.01). Thick ascending limb (T-ALH) function was assessed by measurement of ability to lower perfusate chloride ion concentration (DeltaCl). Following UUO DeltaCl was reduced 76% (-39+/-9 vs. -9+/-1 meq/liter, P < 0.001). Cortical collecting tubule (CCT) function was assessed by measurement of antiduiretic hormone (ADH)-dependent osmotic water flow. Following UUO osmotic water flow was reduced 76% (0.90+/-0.08 vs. 0.22+/-0.04 nl/mm per min, P < 0.01) and this ADH resistance could not be overcome by cAMP. Nephron segments were then examined following relief of BUO. There were no differences in intrinsic function following relief of BUO when compared with UUO. We conclude that in UUO and BUO (a) the intrinsic tubular defects are identical, (b) the natriuresis noted is due, in part, to disordered JMPCT, PST, and T-ALH NaCl reabsorption, (c) the impaired concentrating ability is due, in part, to depressed function in T-ALH and ADH resistance of the CCT, and (d) the ADH resistance occurs at a site distal to the intracellular generation of cAMP.     

Effects of Atrial Impulse Timing on AV Concealed Conduction in the Rabbit Heart

The influence of the timing of a nontrunsmitted or transmitted atrial impulse on the atrioventricular (AV) conduction time of the subsequent impulse was studied in nine isolated rabbit hearts. AV conduction curves were determined by applying the atrial extrasfimulus test. The extrasfimulus was delivered preceded or not by an interposed afrial impulse whose coupling interval with respect to the last atria] beat of a basic train was kept constant at 100, 120, 140, 160, 175, 200, 225, 250, and,300 msec. In all experiments, there was a "concealment interval," i.e., the AV effective refractory period was longer than the atrial functional refractory period, and in seven experiments was comprised between 100 and 160 msec. For any given extrastunulus coupling interval in the presence of an interposed nontransmitted atrial impulse, AV conduction time was significantly greater than in its absence; the increase was greater than the longer the nontransmifted atrial impulse coupling interval, i.e., the shorter the subsequent transmitted impulse coupling interval with respect to the previous interposed nontransmitted impulse. The AV conduction curves relating the extrastimulus AV conduction time to its coupling interval with respect to the last atrial impulse of the basic train fitted to a hyperbolic model both in the absence of the interposed atrial impulse and in its presence (mean square residual 31 ± 23 msec²). and the interposed atrial impulse modified the constants of the functions; the slope of the linear transformations was progressively more negative as the interposed atrial impulse was delayed. Furthermore, the effects of the interposed atrial impulse—transmitted or not—on AV conduction time of the subsequent impulse were qualitatively similar, their magnitude depending on the time elapsed between the two.     

经胸超声心动图对3种兔心力衰竭模型的检测

目的应用经胸超声心动图评价兔3种不同类型心力衰竭模型的效果。方法24只兔随机分成3组,A组急性心肌梗死组,结扎冠状动脉左前降支致前间壁心肌梗死;B组扩张型心肌病组,阿霉素经耳缘静脉给药复制扩心病模型;C组慢性压力后负荷心肌肥厚组,主动脉缩窄法制作心肌肥厚致心力衰竭模型。术后不同时间行心脏超声检查评价造模效果。结果经胸超声可获取兔心脏清晰图像。A组造模成功表现为节段性室壁运动异常和射血分数(EF)减低。B组左心扩大,心功能显著下降,并可出现心包积液。C组先出现心肌肥厚,EF增高,终末期心腔扩大,EF下降。结论应用超声心动图技术活体检测兔心力衰竭模型效果可行。     

Effect of Hypersensitivity on Protein Uptake Across the Air-Blood Barrier of Isolated Rabbit Lungs

In previous studies with isolated perfused rabbit lungs, we observed that human serum albumin (HSA) and ovalbumin, introduced into the isolated lungs as an aerosol, entered the pulmonary circulation antigenically intact. The "inhaled" proteins were also broken down in the lung. When lungs from animals immunized with one protein inhaled the two proteins simultaneously, absorption of intact antigen was specifically reduced, and there was a nonspecific increase in the appearance of metabolites of both proteins in the blood.In the present study, we investigated the antigen-specific and nonspecific effects of two types of hypersensitivity responses on protein absorption across the air-blood barrier of isolated rabbit lungs. In one group of lungs, an acute hypersensitivity response was induced by introducing HSA into the blood perfusing lungs from HSA-immunized rabbits. In another, the rabbits had been previously exposed to chronic HSA aerosol until their lungs exhibited a chronic immunologic inflammatory response. Lungs from both groups were insufflated simultaneously with HSA, and a nonspecific protein, ovalbumin. Lungs in which the acute anaphylactic response was induced showed no alteration in the absorption of either intact protein compared with HSA-immunized controls, but absorbed a somewhat larger quantity of breakdown products of the specific antigen. Lungs undergoing the chronic alveolar inflammation were more permeable to nonspecific protein than were noninflamed lungs. Despite the increased permeability to nonspecific protein, the absorption of antigen was blocked as effectively as in immune but noninflamed controls. In these chronically inflamed lungs, the absorption of antigen breakdown products was enhanced. The results indicate that both immunologic and inflammatory mechanisms may control the amounts of inhaled soluble proteins that reach the blood via the alveolocapillary barrier. Alterations in the absorption of inhaled proteins and their metabolites across the air-blood barrier during certain types of hypersensitivity responses may be of immunologic and pathologic significance.     

三十烷醇对大鼠离体心脏缺血再灌注损伤的影响

【目的】观察三十烷醇（triacontanol ,TRIA）对心肌缺血再灌注损伤（IRI）的影响。【方法】采用Langendorff灌流装置建立大鼠离体心脏IRI模型。将大鼠随机分为正常组、缺血再灌注（IR）组、不同剂量T RIA＋IR组及T RIA （2．5μg/mL）组。正常组全心持续灌流90 min;IR组平衡灌注30 min ,缺血30 min后再灌注30 min;TRIA＋IR组在缺血前5 min分别给予（25,15,5,2．5）μg/mL TRIA之后处理同IR组;TRIA组平衡灌注30 min后给药5 min ,之后持续灌流30 min。观测各组心率（HR）、冠脉流量（CF）、左室内压（LVP）和左室内压变化最大速率（± dp/dtmax）,测定冠脉流出液中肌酸激酶（CK）释放量。【结果】与正常组比较,IR组引起明显的心功能损伤,表现为再灌注期间 HR、CF、LVP、± dp/dtmax降低以及CK释放量增加;心脏灌注不同剂量TRIA（25,15,5,2．5μg/mL）5 min可加重IRI所致心功能损伤,甚至心脏停跳,表现为LVP、± dp/dtmax进一步降低,CF显著减少,HR减慢以及CK释放量增加;单独灌注TRIA（2．5μg/mL）对大鼠心功能也有明显抑制作用,抑制作用持续30 min不能恢复。【结论】离体大鼠心脏灌流 T RIA可抑制心功能及加重心肌IR后心功能的损伤。     

The Ventricular Intracardiac Unipolar Paced-Evoked Potential in an Isolated Animal Heart

The endocardial unipolar paced evoked response has excited a great deal of interest due to its possible use in the measurement of the metabolic state of the body and other pacer-related areas. Although rate-responsive pacing utilizing this signal has been clinically evaluated, little is known regarding the behavior of the components of this waveform under normal physiological conditions. We have developed an electronic circuit which allows the recording of the evoked response within a few milliseconds of a pacing stimulus of 5 V and 0.5 ms duration being applied using a single unipolar, smooth platinum electrode of 14 mm2 surface area. The paced evoked response was measured using a total of 20 isolated rabbit heart preparations. Five were run for 8 hours and the remaining fifteen were run for 5 hours. Our results indicate that the waveform components of the evoked response remain stable while the preparation is viable, but that two of the time-related measurements change with loss of viability. A significant lengthening of the stimulus-R interval was seen together with a dramatic shortening of the R-T period. The net result of these changes was an overall reduction of 17% in the complex duration. In addition, we found the R-T shortening to be a sensitive measure of myocardial integrity. We conclude that the combination of our interface charge elimination circuit and the isolated heart preparation has proved a useful system for the investigation of the paced evoked potential. Furthermore, the loss of myocardial viability has a complex action on this response.     

Pharmacokinetics of Nisoldipine Coat--Core Formulation in Subjects with Liver Cirrhosis

The pharmacokinetics of a controlled-release formulation (coat--core) of the calcium channel blocker nisoldipine was investigated in eight subjects with biopsy-proved liver cirrhosis and eight healthy subjects. In Stage I, subjects received a single 10-mg dose to determine if this dose would be safely tolerated in the subjects with cirrhosis. Because all subjects in both groups tolerated the dose without difficulty, all were continued to Stage II. In Stage II, subjects received a once-daily dose of 10-mg coat-core tablets for 7 days. Serial plasma samples were assayed for nisoldipine in both stages. The C(max) and AUC of nisoldipine were approximately fourfold to fivefold higher (p < 0.01) in subjects with cirrhosis as compared to healthy subjects; however, there was overlap in the range of pharmacokinetic parameters between the two groups. The accumulation factor following multiple dosing was similar in both groups. Results suggest that nisoldipine dose should be optimized by monitoring of a pharmacodynamic end point, such as effect on blood pressure. It is likely that dose requirements for patients with liver disease will be lower.     

Digoxin's Minimal Inotropic Effect Is Not Limited by Sodium-Calcium Exchange in the Intact Immature Rabbit Heart

BACKGROUND: In the intact immature heart, how much digoxin can drive sodium-calcium exchange has not been studied in the context of sodium-calcium exchanger abundance. METHODS AND RESULTS: The effects of digoxin and low potassium on contractility in the intact, paced and isovolumically contracting immature rabbit heart were studied in both the absence and presence of L-type calcium channel blockade. Without calcium channel blockade, digoxin increased contractility minimally and only at 10(_6) M/L. In contrast, low potassium (2.2 mM/L) substantially increased contractility in all experiments, a result indicating abundant sodium-calcium exchanger activity. During nifedipine-induced calcium channel blockade, digoxin (10(_6) M/L) allowed modest recovery of contractility, whereas digoxin and low potassium together allowed complete recovery as assessed by dP/dt(max); however, all hearts so perfused subsequently developed ventricular fibrillation, presumably because of calcium overload. CONCLUSIONS: In intact immature rabbit heart, digoxin can drive sodium-calcium exchange and thus increase contractility to only a minimal extent. This effect does not appear to be limited by intrinsic exchanger activity, which appears abundant in this preparation. Rather, digoxin's inability to drive the sodium-calcium exchanger may be due to developmental differences in binding to the sodium pump. The sodium-calcium exchanger itself seems capable not only of providing enough intracellular calcium for normal contraction, but also of overloading the myocardium with calcium, despite L-type calcium channel blockade.     

腺苷对家兔心脏房室结区不同细胞的动作电位的影响

为探讨房室交界区各部位的电生理特性以及腺苷对各部位的动作电位特性的影响，本文对20只家兔制作了房室结立体标本，用标准微电极技术法记录了不同部位房结区（AN）、结区（N）、结希区（NH）以及冠状窦口周围和三尖瓣，二尖瓣房室环上的动作电位形态及腺苷对其的影响。结果表明似房结区，似结区及似结希区的动作电位图形分布广泛，除在传统的房室结可记录到此组动作电位图形外，在冠状窦及房室环周围也可记录到类似图形。腺苷对各区细胞的作用也明显不同，其共同的作用为缩短动作电位时程，减慢心率。结果提示房室交界区或称为广义的房室结是一结构和功能复杂的结合体，对其结构和功能结合起来研究才能真正了解其电生理特性。     

高胆固醇血症家兔心脏单相动作电位及钙电流的特征

目的观察高胆固醇血症对家兔心脏单相动作电位及钙电流的影响。方法24只家兔分为高胆固醇饮食组和对照组各12只,分别给予高胆固醇饲料和标准饲料饲养10周后,检测血脂、心电图和室颤阈值,记录离体灌流心脏单相动作电位,并记录心室肌细胞的L型钙通道电流。结果高胆固醇饮食组兔的血脂水平明显高于对照组(P<0.01);室颤阈值(10.2±1.7)V,低于对照组的(13.9±1.3)V(P<0.05);单相动作电位复极90%的时程(MAPD90)较对照组延长并呈更明显的逆频率依赖性,在1500ms起搏时MAPD90为(348±21)ms,而对照组为(271±16)ms;心室肌细胞的L型钙通道电流密度为(14.7±0.8)pA/pF,明显高于对照组的(10.9±1.1)pA/pF(P<0.01)。结论高胆固醇血症家兔的心脏单相动作电位及心肌细胞L型钙通道电流明显改变,复极时程延长,室颤阈值降低。     

Atrioventricular Electrotonic Interaction in Complete Atrioventricular Block: An Experimental Model Using Radiofrequency Energy in the Rabbit Heart

Provided the conditions for electrotonic transmission exist, an automatic focus surrounded by a block zone may be externally modulated. The atrioventricular (AV) electrotonic interaction was studied in 16 perfused rabbit hearts with supra-Hisian complete AV block induced using low radiofrequency energy doses (2.5 watts; 10 seconds). In nine experiments the sinus node was preserved (group I), whereas in seven it was removed maintaining an AV nodal rhythm (group II). The V-V (ventricular cycle length) and V-A (coupling of the intervening atrial beat) in both groups, and also the A-A (atrial cycle length) and A-V (coupling of the intervening ventricular beat) intervals in group II, were measured beat by beat after current delivery. The phase response curves V-V versus V-A, and A-A versus A-V showed AV interaction in five experiments from group I, and in four from group II, as follows: (1) accelerating phase response curve, characterized by a pacemaker acceleration (V-V or A-A abbreviation) at a critical V-A or A-V coupling interval; maximum acceleration could be progressively (phase response curve without rapid cross-over) or briskly (phase response curve with rapid crossover) reached; from this point onwards acceleration decreased with a further increase in V-A or A-V coupling interval (acceleration slope). (2) Biphasic phase response curve, characterized by initial delaying and late accelerating phases. Maximum acceleration and the acceleration slope were both smaller in accelerating phase response curves without rapid cross-over. On reverting complete block in two experiments, a progressive increase in maximum acceleration and acceleration slope was observed. Conclusions: (1) AV interaction in complete AV block can be manifested as accelerating or biphasic phase response curves; (2) transition from electrotonic interaction to conduction seems to be a continuum.