Spontaneous and inducible ventricular arrhythmias in a canine model of chronic heart failure: relation to haemodynamics and sympathoadrenergic activation.

The relationship between the incidence, frequency and complexity of spontaneous ventricular arrhythmias and the extent of haemodynamic compromise and sympathoadrenergic hyperactivity was evaluated in a canine model of chronic heart failure produced by multiple sequential intracoronary microembolizations. Ambulatory ECG Holter monitoring recorded during chronic heart failure in 18 dogs revealed spontaneous ventricular arrhythmias ranging from single ventricular premature beats (VPBs) to non-sustained episodes of ventricular tachycardia (VT). Single VPBs were present in 94% of dogs, couplets in 67%, triplets in 28% and spontaneous episodes of non-sustained VT in 33%. Dogs with > 28 VPBs.h-1 (n = 9) had a markedly higher plasma norepinephrine (PNE) concentration (1001 +/- 185 vs 561 +/- 31 pg.ml-1) (P < 0.03), and a higher pulmonary artery wedge pressure (PAWP) (18 +/- 2 vs 12 +/- 1 mmHg) (P < 0.03) than dogs with < or = 28 VPBs.h-1 (n = 9). Dogs that developed spontaneous episodes of VT also had significantly higher PNE levels (1119 +/- 247 pg.ml-1) compared to dogs that did not develop VT (612 +/- 64 pg.ml-1) (P < 0.02). Programmed ventricular stimulation performed in seven of 18 dogs resulted in the development of sustained monomorphic VT in three and ventricular fibrillation in three dogs each (43%, 43%). Dogs with inducible sustained monomorphic VT had a significantly higher number of ambient arrhythmias and higher PAWP compared to dogs that did not develop sustained VT. The observed complexity, frequency and incidence of spontaneous and inducible ventricular arrhythmias in this canine model are similar to those described in patients with chronic heart failure.     

卡维地洛对老年慢性心力衰竭合并室性心律失常患者血清肾上腺素受体自身抗体的影响

目的 研究卡维地洛对老年慢性心力衰竭(心衰)合并室性心律失常(室律失常)患者血清抗β1、β2和α1肾上腺素受体自身抗体的影响.方法 将68例老年冠心病心衰合并有室律失常的患者随机分为两组,在常规强心利尿治疗的同时,一组给予美托洛尔、另一组给予卡维地洛治疗,检测两组治疗前和治疗后6个月心脏超声、B型利钠肽(BNP)、动态心电图和抗β1、β2和α1受体自身抗体阳性率的改变,同时检测治疗前后血压、心率、肝和肾功能的变化.结果 与治疗前相比,两组均使心衰患者的基础心率和BNP下降,左室射血分数(LVEF值)升高,心脏功能得到改善;与美托洛尔组相比,卡维地洛治疗后收缩压和BNP下降更明显,差异有统计学意义(P<0.01).美托洛尔治疗后,可使患者血清中抗β1受体自身抗体的阳性率下降(P<0.05),而对抗β2和α1 受体自身抗体的阳性率没有影响(P>0.05).卡维地洛治疗后,血清中抗β1、β2和α1受体自身抗体的阳性率均明显下降(P<0.01),室律失常的发生率也比美托洛尔治疗组明显下降(P<0.01).结论 对老年冠心病慢性心衰合并室律失常患者,应用卡维地洛比美托洛尔能更有效地降低室律失常的发生.     

Influence of the force--frequency relationship on haemodynamics and left ventricular function in patients with non-failing hearts and in patients with dilated cardiomyopathy

In isolated human myocardium it was shown that a positive force-frequencyrelationship occurs in non-failing myocardium; however, theforce-frequency relationship was found to be inverse in myocardiumfrom failing human hearts. In order to investigate the clinicalrelevance of these experimental findings, the influence of heartrate changes on haemodynamics and left ventricular functionwas studied in eight patients without heart failure and in ninewith failing dilated cardiomyopathy (NYHA II–III). Rightventricular pacing was performed at a rate slightly above sinusrate and at 100, 120 and 140 beats. min^–1 Haemodynamicparameters were obtained by right heart catheterization andby high-fidelity left ventricular pressure measurements. Leftventricular angiography was performed at basal pacing rate andat 100 and 140 beats. min^–1 With increasing heart rate,cardiac index increased in patients with normal left ventricularfunction from 2·9 ± 0·2 to 3·5 ±0·21. min^–1. m^–2 (P<0·01) and decreasedcontinuously in patients with dilated cardiornyopathy from 2·6± 0·1 to 2·2 ± 0·11. min^–1. m^–2 (P<0·05). With increasing heart rate,the maximum rate of left ventricular pressure rise increasedin non-failing hearts from 1388 ± 86 to 1671 ±88 mmHg. s^–1 (P<0·01) and did not change infailing hearts. Ejection fraction decreased from 27 ± 3% to 19 ±2% in patients with dilated cardiomyopathy (P<0·05)when the pacing rate was changed from 84 ± 2 beats. min^–1to 140 beats. min^–1, which was associated with a significantlyincrease in end-systolic volume without significantly changesin end-diastolic volume. In patients with normal left ventricularfunction, when the pacing rate was changed from 85 ±3 beats. min^–1 to 140 beats. min^–1, end-diastolicvolume decreased significantly by 13%, whereas left ventricularend-systolic volume and ejection fraction did not significantlychange. Left ventricular systolic and end-diastolic pressuresdid not significantly change with pacing tachycardia in eithergroup. The frequency-related changes in left ventricular volumesand pressures indicate that the differrent haemodynamic effectsof pacing tachycardia in both groups of patients result predominantlyfrom frequency effects on myocardial function and not from frequencyeffects on preload or afterload. These data indicate that recentexperimental findings of positive force-frequency effects innon-failing and negative force-frequency effects in failinghuman myocardium are relevant for the intact heart.     

Cardiac oufflow of endothelin, neuropeptide Y and noradrenaline in relation to hyperaemia in coronary sinus flow following electrical conversion of induced ventricular fibrillation in man

The implanted cardioverter defibrillator represents an alternativetherapy for patients with drug-refractory nialignant ventriculararrhythmios. Implantation and testing of the device requiresthat ventricular fibrillation be evoked and converted, thusproviding a situation in which cardiovascular haemodynamicscan be studied In this study we have evaluated the effects ofelectrically induced ventricular fibrillation, followed by defibrillation,on coronary sinus blood flow and cardiac outflow of endothelin-and neuropeptide Y-like immunoreactivity (-LI) and of noradrenaline.Twelve patients were studied during implantation of a defibrillator.Ventricular fibrillation was induced and terminated after 17± 1 s 5 ± 1 times in each patient. In six patientscoronary sinus blood flow was measured continuously. Plasmasamples were obtained from four of these patients and anothersix patients, from the coronary sinus, radial artery and centralvein before and during fibrillation and at two time points (<30sand 5 min). Basal coronary sinus blood flow decreased to 38%at 14 ±2 s of ventricular fibrillation. Immediately followingdefibrillation there was a short-lasting increase in coronarysinus blood flow to 244% and a significant increase in the levelsof neuropeptide Y-LI (146%) and noradrenaline (158%) in thecoronary sinus while endothelin-LI remained unchanged (97%).Neither fibrillation nor defibrillation evoked any changes inthe peripheral arterial and venous levels of endothelin-, neuropeptideY-LI or noradrenaline. It is concluded that coronary sinus bloodflow is markedly reduced during fibrillation and that restorationof normal impulse activity is followed by short-lasting hyperaemia.There was no evidence for effects on the vascular endotheliumas assessed by endothelin levels.     

Cardiac oufflow of endothelin, neuropeptide Y and noradrenaline in relation to hyperaemia in coronary sinus flow following electrical conversion of induced ventricular fibrillation in man

The implanted cardioverter defibrillator represents an alternativetherapy for patients with drug-refractory nialignant ventriculararrhythmios. Implantation and testing of the device requiresthat ventricular fibrillation be evoked and converted, thusproviding a situation in which cardiovascular haemodynamicscan be studied In this study we have evaluated the effects ofelectrically induced ventricular fibrillation, followed by defibrillation,on coronary sinus blood flow and cardiac outflow of endothelin-and neuropeptide Y-like immunoreactivity (-LI) and of noradrenaline.Twelve patients were studied during implantation of a defibrillator.Ventricular fibrillation was induced and terminated after 17± 1 s 5 ± 1 times in each patient. In six patientscoronary sinus blood flow was measured continuously. Plasmasamples were obtained from four of these patients and anothersix patients, from the coronary sinus, radial artery and centralvein before and during fibrillation and at two time points (<30sand 5 min). Basal coronary sinus blood flow decreased to 38%at 14 ±2 s of ventricular fibrillation. Immediately followingdefibrillation there was a short-lasting increase in coronarysinus blood flow to 244% and a significant increase in the levelsof neuropeptide Y-LI (146%) and noradrenaline (158%) in thecoronary sinus while endothelin-LI remained unchanged (97%).Neither fibrillation nor defibrillation evoked any changes inthe peripheral arterial and venous levels of endothelin-, neuropeptideY-LI or noradrenaline. It is concluded that coronary sinus bloodflow is markedly reduced during fibrillation and that restorationof normal impulse activity is followed by short-lasting hyperaemia.There was no evidence for effects on the vascular endotheliumas assessed by endothelin levels.     

冠状动脉介入治疗对心肌梗死患者室壁瘤逆转和心功能的影响

目的 探讨不同时间段行经皮冠状动脉介入治疗(PCI)对急性心肌梗死(AMI)后左心室室壁瘤(LVA)形成的逆转效应及其对心功能的影响.方法 选择2001年1月至2004年7月我院收治的首次前壁AMI患者,经导管法左心室造影确定合并室壁瘤者共326例,根据AMI发病后行PCI的时间分为:发病≤3 h组、4～6 h组、7～12 h组和1周组(发病时间≥13 h且小于1周),4组患者于PCI后即行导管法左心室造影,测定心室容积、压力参数和室壁运动积分;PCI术后1周时行平衡法核素心室造影,测定反常室壁容积指数;6个月时重复上述检查,并随访3年,记录主要心脏事件(MACE)的发生率. 结果 PCI术后6个月随访,发病≤3 h组、4～6 h组、7～12 h组、1周组左心室舒张末期容积指数、左心室收缩末期容积指数、左心室室壁运动积分、左心室舒张末期压力均较行PCI时降低(均P<0.05),而左心室射血分数较前增高(P<0.05),其中发病≤3 h组变化最为显著.PCI术后6个月,发病≤3 h组反常室壁容积指数明显低于4～6 h组、7～12 h组、1周组,分别为:(12.1±2.1)%与(15.4±2.4)%、(16.5±2.5)%、(20.4±3.7)%,均P<0.05.住院期间及术后3年随访,≤3 h组、4～6 h组、7～12 h组3组MACE发病率低于1周组,3年随访时病死率均低于1周组(分别为2.8%、3.0%、3.1%与17.9%,均P<0.05). 结论 对AMI患者越早期开通梗死相关动脉,越能有效地抑制并逆转LVA的形成,提高左心室功能,改善患者的预后.     

急性心肌梗死后择期冠脉介入治疗对左室重构和心功能的影响

目的探讨急性心肌梗死（AMI）后择期经皮冠状动脉介入（PCI）治疗对左心室重构和心功能的影响。方法112例AMI患者,分为PCI组和药物治疗组,PCI组于发病后1～2周内行PCI治疗,所有患者于发病后1～2周时、4周和24周时行超声心动图（UCG）检查,观察左心室收缩末容积指数（LVESVI）、左心室舒张末容积指数（LV-EDVI）和左室射血分数（LVEF）。结果行PCI治疗后,血管再通率为100%,术后4周和24周的LVESVI、LVEDVI和LVEF均明显优于术前,与药物治疗组比较有显著性差异（P<0.05）。结论AMI后择期PCI治疗能够有效抑制左心室重构,改善心功能。     

Effects of adrenaline on electrophysiological parameters during short exposure to global ischemia. A ventricular fibrillation study in isolated heart

Background. The mechanisms by which adrenaline may enhance defibrillation success rate, is poorly understood. Objectives. To study electrophysiological effects of adrenaline during short exposure to global ischemia. Methods. In isolated perfused feline hearts, coronary perfusion was eliminated repeatedly for 1 min with 10 min reperfusion intervals. Treatment included: (1) continuous perfusion alone—control, (2) global ischemia alone, (3) adrenaline (10^–7 M) during perfusion, (4) adrenaline (10^–7 M) during global ischemia (n = 10), in separate hearts, (5) control and higher adrenaline concentration (1 × 10^–6 M), (6) during perfusion, (7) during global ischemia (n = 9). Measurements during pacing included: (1) diastolic threshold of excitability; (2) refractoriness; (3) epicardial conduction time; and (4) all tissue resistivity to indirectly detect changes in passive properties of conduction. Measurements during 1 min (or 90 sec) of electrically induced ventricular fibrillation included—all tissue resistivity and, based on maximal entropy spectral analysis and normalized entropy, rate of arrhythmia and degree of arrhythmia organization. Results. Adrenaline (10^–7 M) during global ischemia vs control caused spontaneous arrhythmia termination, increased threshold significantly but reduced conduction time. Higher adrenaline concentration (1 × 10^–6 M) during global ischemia improved the passive properties of conduction and arrhythmia organization and reduced arrhythmia rate. Global ischemia alone increased conduction time but had a deleterious effect on passive properties. Adrenaline (10^–7 M) during perfusion improved conduction, but did so less than during global ischemia. Higher adrenaline concentration during perfusion (10^–6 M) improved arrhythmia organization and caused spontaneous arrhythmia termination but again less than during global ischemia. Conclusions. During short periods of global ischemia adrenaline improved the passive properties of conduction and arrhythmia organization, reduced arrhythmia rate and increased its spontaneous termination. Such changes may be operative in improving defibrillation success.     

Effects of oral digoxin on ventricular ectopy and its relation to left ventricular function

The ventricular antiarrhythmic properties of oral digoxin were examined in 13 patients with chronic ventricular ectopy using serial 24-hour electrocardiographic monitoring. Mean premature ventricular complex frequency (per 1,000 normal beats) decreased from 56 +/- 47 during the placebo period to 40 +/- 27 (p = not significant [NS]) and 25 +/- 17 (p less than 0.05) during daily administration of digoxin, 0.25 and 0.375 mg. Digoxin had no significant effect on the qualitative occurrence of complex ventricular arrhythmia patterns (multiformity, bigeminy, couplets, ventricular tachycardia). Radionuclide left ventricular (LV) ejection fraction was measured during the placebo period. Seven patients had normal (ejection fraction greater than 50%) and 6 abnormal global LV performance. In the normal group, the mean premature ventricular complex frequency decreased from 69 +/- 58 to 20 +/- 18 (p less than 0.05) and the mean couplet frequency decreased from 0.59 +/- 0.85 to 0.07 +/- 0.06 (p less than 0.04) during the placebo and 0.375 mg digoxin dosing periods, respectively. In contrast, no significant changes in either variable occurred after digoxin in subjects with depressed LV function. This study indicates that oral digoxin is moderately effective in suppressing premature ventricular complexes, and that its effects are greatest in patients with normal overall LV performance.     

冠状动脉侧支循环对其病变程度与左室功能关系的影响

目的探讨冠心病患者冠状动脉病变程度与左室功能的关系。方法３６例选择性冠状动脉造影主要分支狭窄≥７０％的患者作Ｌｅａｍａｎ冠状动脉记分，左室造影测左室射血分数（ＬＶＥＦ），左室壁运动作Ｃｏｒｔｉｎａ记分，研究侧支循环对Ｌｅａｍａｎ冠状动脉记分与ＬＶＥＦ及Ｃｏｒｔｉｎａ记分间关系的影响。结果全组Ｌｅａｍａｎ冠状动脉记分与ＬＶＥＦ及Ｃｏｒｔｉｎａ左室壁运动记分无相关，但在无侧支循环建立的亚组，Ｌｅａｍａｎ冠状动脉记分与ＬＶＥＦ呈负相关（ｒ＝－０．６４，Ｐ＜０．０１），与Ｃｏｒｔｉｎａ左室壁运动记分呈显著正相关（ｒ＝０．７３，Ｐ＜０．０１）。结论冠状动脉病变程度与左室功能间的关系取决于严重病变的冠状动脉有无建立侧支循环。侧支循环的建立对冠心病患者的左室功能有保护作用。     

Effects of quinapril on myocardial function,ventricular remodeling and cardiac cytokine expression in congestive heart failure in the rat

Inflammatory cytokines have been shown to be activated in congestive heart failure (CHF). This activation is likely the result of the convergence of a number of factors, several of which could be attenuated with the use of an Angiotensin converting enzyme (ACE) inhibitor. In order to assess this, rats had a myocardial infarction (MI) created by coronary artery ligation and were followed for 28 days without treatment to permit the development of CHF. At that time, the ACE inhibitor quinapril was started, or rats remained untreated and were followed a further 56 days for a total of 84 days. Half of the untreated rats had quinapril started 3 days prior to sacrifice, on day 81. Starting quinapril at either 28 or 81 days had little effect on cardiac hemodynamics, or ventricular remodeling. Quinapril did however attenuate the MI-induced rise in cardiac cytokine expression (tumor necrosis factor- [TNF-], interleukin-1, -5 and -6). Thus, in CHF, ACE inhibitors attenuate the rise in cardiac cytokine expression. This study helps to identify a new mechanism by which ACE inhibitors may exert their beneficial effects in CHF.     

Effects of levocarnitine on cardiac function,urinary albumin,hs-CRP,BNP, and troponin in patients with coronary heart disease and heart failure

ObjectiveTo investigate the effects of levocarnitine on cardiac function, urinary albumin (ALB), high-sensitivity C-reactive protein (hs-CRP), brain natriuretic peptide (BNP), and troponin in patients with coronary heart disease (CHD) and heart failure (HF).MethodsIn total, 246 patients with CHD-caused HF were selected and randomly divided into Group A and Group B. A fully automatic biochemical analyzer was used to measure the levels of ALB, hs-CRP, BNP, and troponin in both groups of patients, and the expression levels of LVDD and LVEF were detected by cardiac color ultrasonography. Patients in Group B were intravenously injected with 3.0 g of levocarnitine, once per day. After 14 days, changes in levels of ALB, hs-CRP, BNP, troponin, LVDD, and LVEF in Group A patients were detected.ResultsThe effective cure rates of patients in both groups were 65.8% and 81.3%, respectively, and there was a statistically significant difference between the two groups (p < 0.05). After administration of levocarnitine, all indicators showed decreasing trends, but the LVEF level increased. Among them, patients treated with levocarnitine showed the most evident decrease in LVEF. Decrease in BNP was the largest (p < 0.05). Additionally, there was no statistical difference in incidence rate between the two groups (5.8% vs. 2.5%, p = 0.222).ConclusionLevocarnitine can effectively improve ALB, hs-CRP, BNP, troponin, and LVDD levels to improve cardiac function rating and thus improve cardiac function.     

Effect of isosorbide dinitrate on cardiac output in severe cardiac failure: relation to initial hemodynamics, ventricular volume, and the preload reserve mechanism

Isosorbide dinitrate (ISDN) improves the clinical and hemodynamic state of patients with heart failure, but may cause dizziness and syncope. To characterize patients in whom cardiac output falls with high-dose nitrate therapy and to examine further the pathophysiology of the fall in cardiac output in these patients, we studies the effect of sublingual ISDN on forward cardiac output in 14 patients with severe cardiac failure (New York Heart Association grades 3-4). We examined systolic and diastolic left ventricular (LV) function from pressure and volume analyses of LV function. After administration of 15 mg ISDN, cardiac output was either unaltered or increased in 7 patients (Group 1) (11 +/- 12%, mean +/- SD), and decreased in 7 (Group 2) (-13 +/- 10%) (Group 1 vs. 2, p less than 0.002). Initial systemic arterial pressure, LV ejection fraction, wedge and LV transmural filling pressures were similar in both groups, but Group 2 patients had a lower systemic vascular resistance (p = 0.07) and tended to have a larger initial LV end-diastolic volume and increased end-diastolic compliance; following ISDN the decrease in LV filling pressure and end-diastolic volume was larger and the product of the changes greater (p less than 0.02). Thus ISDN decreases filling pressure and improves forward cardiac output in some patients with congestive heart failure, but large doses may decrease cardiac output in a subset of patients who have a lower systemic vascular resistance and a larger more compliant ventricle, maintaining forward blood flow predominantly by a preload reserve mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)     

辛伐他汀对心力衰竭患者心脏功能及左心室重构的影响

目的观察小剂量辛伐他汀对心力衰竭患者心脏功能及左心室重构的影响。方法选取2008年1月至2009年7月东莞市人民医院确诊为非缺血性心力衰竭的患者61例为研究对象。按电脑随机数字表法将入选对象分为观察组（n=30）与对照组（n=31）,观察组在标准心力衰竭治疗基础上加服辛伐他汀（20mg／d,治疗期6个月）。比较两组治疗前后患者心脏功能、生化指标的变化。结果经过6个月的治疗,观察组纽约心脏协会心功能分级[（2．0±0．4）级vs．（2．5±0．4）级,P〈0．01]和左心室射血分数（58．7％±5．2％眠43．0％±5．7％,P〈0．01）显著改善,差异有统计学意义;对照组纽约心脏协会心功能改善,差异有统计学意义[（2．1±0．4）级vs．（2．4±0．4）级,P〈0．05];左心室射血分数有改善的趋势,但差异无统计学意义（47．6％±5．3％vs．40．9％±6．3％,P=0．052）。结论非缺血性心力衰竭患者在标准心力衰竭治疗的基础上加用辛伐他汀治疗安全、有效,可显著改善该类患者左心室重构与心功能状态。     

Effects of ganglionated plexi ablation on ventricular electrophysiological properties in normal hearts and after acute myocardial ischemia

Background

Ganglionated plexi (GP) ablation has been shown to play an important role in atrial fibrillation (AF) initiation and maintenance. Also, GP ablation increases chances for prevention of AF recurrence. This study investigated the effects of GP ablation on ventricular electrophysiological properties in normal dog hearts and after acute myocardial ischemia (AMI).

Methods

Fifty anesthetized dogs were assigned into normal heart group (n = 16) and AMI heart group (n = 34). Ventricular dynamic restitution, effective refractory period (ERP), electrical alternans and ventricular fibrillation threshold (VFT) were measured before and after GP ablation in the normal heart group. In the AMI heart group, the incidence of ventricular arrhythmias and VFT were determined.

Results

In the normal heart group, GP ablation significantly prolonged ERP, facilitated electrical alternans but did not increase ERP dispersion, the slope of restitution curves and its spatial dispersion. Also, GP ablation did not cause significant change of VFT. In the AMI heart group, the incidence of ventricular arrhythmias after GP ablation was significantly higher than that in the control group or the GP plus stellate ganglion (SG) ablation group (P < 0.05). Spontaneous VF occurred in 8/12, 1/10 and 2/12 dogs in the GP ablation group, the GP plus SG ablation group and the control group, respectively (P < 0.05). VFT in the GP ablation group showed a decreased trend though a significant difference was not achieved compared with the control or the GP plus SG ablation group.

Conclusions

GP ablation increases the risk of ventricular arrhythmias in the AMI heart compared to the normal heart.     

右室流出道间隔部与心尖部起搏对完全性CHB患者心功能的影响

目的:比较右室流出道间隔部(RVOTS)起搏与右室心尖部(RVA)起搏对完全性房室传导阻滞(CAVB)患者心功能的影响。方法:50例CAVB患者被随机分为RVOTS组(25例)和RVA组(25例),全部植入房室全能(DDD)型起搏器,分别观察术前,术后6个月、12个月的左室射血分数(LVEF)及左室短轴缩短率(FS)的变化。结果:所有患者以DDD模式或心房同步心室抑制(VDD)模式起搏,心室起搏比例为100%。所有患者均完成1年随访。术后6个月两组LVEF、FS无显著差异(P均>0.05);术后12个月,ROVTS组LVEF[(57.29±2.87)%比(50.03±2.98)%]、FS[(34.24±2.59)%比(29.06±3.72)%]显著优于RVA组(P均<0.05)。结论:右室流出道间隔部起搏的左室收缩功能显著好于右室心尖部起搏。     

居家心脏康复和中心心脏康复对冠心病患者心肺适能的影响

目的 探索居家心脏康复(HBCR)和中心心脏康复(CBCR)对冠心病(CHD)患者心肺适能的影响.方法 选取2018年11月至2019年10月在解放军总医院心脏康复中心门诊就诊的18～80岁的CHD患者,采用随机数表和信封法将患者分为HBCR组和CBCR组,分别以HBCR或CBCR干预3个月.对比2组患者干预前后的峰值...     

Effects of KATP channel openers diazoxide and pinacidil in coronary-perfused atria and ventricles from failing and non-failing human hearts

This study compared the effects of ATP-regulated potassium channel (K_ATP) openers, diazoxide and pinacidil, on diseased and normal human atria and ventricles. We optically mapped the endocardium of coronary-perfused right (n = 11) or left (n = 2) posterior atrial-ventricular free wall preparations from human hearts with congestive heart failure (CHF, n = 8) and non-failing human hearts without (NF, n = 3) or with (INF, n = 2) infarction. We also analyzed the mRNA expression of the K_ATP targets K_ir6.1, K_ir6.2, SUR1, and SUR2 in the left atria and ventricles of NF (n = 8) and CHF (n = 4) hearts. In both CHF and INF hearts, diazoxide significantly decreased action potential durations (APDs) in atria (by − 21 ± 3% and − 27 ± 13%, p < 0.01) and ventricles (by − 28 ± 7% and − 28 ± 4%, p < 0.01). Diazoxide did not change APD (0 ± 5%) in NF atria. Pinacidil significantly decreased APDs in both atria (− 46 to −80%, p < 0.01) and ventricles (− 65 to − 93%, p < 0.01) in all hearts studied. The effect of pinacidil on APD was significantly higher than that of diazoxide in both atria and ventricles of all groups (p < 0.05). During pinacidil perfusion, burst pacing induced flutter/fibrillation in all atrial and ventricular preparations with dominant frequencies of 14.4 ± 6.1 Hz and 17.5 ± 5.1 Hz, respectively. Glibenclamide (10 μM) terminated these arrhythmias and restored APDs to control values. Relative mRNA expression levels of K_ATP targets were correlated to functional observations. Remodeling in response to CHF and/or previous infarct potentiated diazoxide-induced APD shortening. The activation of atrial and ventricular K_ATP channels enhances arrhythmogenicity, suggesting that such activation may contribute to reentrant arrhythmias in ischemic hearts.     

Effects of streptozotocin-induced diabetes and noradrenaline infusion on cardiac output and its regional distribution in pithed rats

Summary ⁴⁶Sc-and ^99mTc-labelled microspheres were used to measure the effects of noradrenaline infusion on cardiac output and its regional distribution in 10 control and 10 streptozotocin-diabetic pithed rats. Plasma noradrenaline concentrations during the infusion were similar in both groups. Pressor responses were significantly smaller in the diabetic animals (controls: + 79, diabetic: +44mmHg; p<0.001). Cardiac output remained similar in both groups before and during the noradrenaline infusion. Total peripheral resistance was similar in both groups before noradrenaline but the noradrenaline-mediated increase was significantly smaller in the diabetic animals (controls: +150%, diabetic: + 76%; p<0.05). Noradrenaline-mediated resistance increases were significantly reduced in several tissues of the diabetic rats including the small intestine (controls: + 132%, diabetic: –4%; p<0.005), the large intestine (controls: +150%, diabetic: +39%; p<0.05) and the kidneys (controls: +180%, diabetic: + 27%;p<0.05), but were very similar in other areas, e.g. in the hindlimbs and tails.