Fructose-1,6-diphosphate in the treatment of chronic heart failure

Fructose-1,6-diphosphate (FDP) was given to 30 patients with chronic heart failure (CHF) caused by various kinds of heart diseases with the purpose to evaluate the effects of FDP on CHF patients. Definite hemodynamic and clinical improvement has been found in this group. CO increased by 1.61 +/- 0.31 L/Min (35%) (P less than 0.01) PCWP decreased by 5.5 +/- 1.08 mmHg (31%); mean PAP decreased by 5.8 +/- 2.07 mmHg (P less than 0.05). EF increased by 6.9 +/- 1.5 (15.1%) as shown by echocardiography and the peak effect of the drug appeared at 2 hours after administration. The results showed that FDP is effective in the treatment of heart failure, especially in patients with dysfunction of other organs.     

Reproducibility of myocardial ischemia induced by atrial stimulation

Reproducibility of myocardial ischemia induced by atrial pacing (P) was investigated in 25 patients (pts) without previous anterior myocardial infarction and showing a positive exercise stress test. The second period of atrial pacing (P2) was exerted 20 minutes after the first (P1). During P2, a reduction in the parameters reflecting myocardial oxygen requirements (maximal left ventricular pressure, dp/dt max, TTI*HR values) was noted, while the signs of ischemia were less pronounced (ST depression decreasing from 2.3 +/- 1 mm to 1.6 +/- 1.0 mm; % of lactate extraction (%L) decreasing from - 6.4 +/- 25.5 to + 8.5 +/- 19.2; p less than 0.5). The 25 pts were divided into 2 groups according to the ejection fraction (EF greater than .55 16 pts Gr.F+; EF less than .55 9 pts Gr.F-). The distribution of coronary lesions was the same for the 2 groups. During P1 GR.F+ registered a negative % L as opposed to Gr.F-. During P2, the difference in the % L between the 2 groups was also significant (2.6 +/- 19.9% F+ vs 18.9 +/- 14.3% F-; p less than .05). Collateral circulation had no effect upon the results, neither for P1 or P2. This study shows that a second period of atrial pacing, 20 minutes after the first, induced lesser ischemia than the first period of atrial pacing. This phenomenon could explain the paradoxical improvement observed in certain patients after a first episode of angina. These results have implications as regards the necessity of double blind studies compared to placebo when using this technique in the evaluation of the effects of anti-ischemic drugs.     

Differential electrocardiographic effects of myocardial ischemia induced by atrial pacing in dogs with various locations of coronary stenosis

The spatial distribution of abnormal repolarization potentials caused by regional myocardial ischemia was determined in 45 dogs. Ameroid constrictors were placed around the left circumflex artery in 10, the left anterior descending artery in 10, and the right coronary artery in 10. Ten dogs without constrictors served as controls. Electrocardiographic events were determined from body surface isopotential distributions, which were computed from potentials sensed by 84 torso electrodes. In control dogs, pacing to heart rates of 230 to 250 beats/min increased the intensity of positive and negative surface extrema during the ST segment without altering their spatial features. Two weeks after placement of the ameroid constrictors, tachycardia induced abnormal negative potentials during the ST segment. Localization of these ischemic forces varied with the placement of the constrictor in a manner consistent with the affected perfusion territories. However, much of the torso surface was involved by all lesions, and only small zones of ST segment depression unique to specific lesions could be identified. In five additional dogs a constrictor was placed on the right coronary artery 3 months after implantation of a device on the circumflex vessel. ST segment patterns during pacing in dogs with two lesions were consistent with the sum of the two individual lesions. Thus, the regional nature of myocardial ischemia is detectable in the body surface isopotential distributions, but the degree of spatial overlap may limit the value of such techniques in extending the usefulness of clinical exercise-stress electrocardiography.     

Fructose 1,6-diphosphate alleviates myocardial ischemia reperfusion injury in rats through JAK2/STAT3 pathway

Objective: To study the effect of fructose 1,6-diphosphate(FDP) on myocardial ischemia reperfusion injury in rats and its molecular mechanism.Methods: Male SPF SD rats were selected as experimental animals and randomly divided into four groups.Sham group received sham operation, I/R group were made into myocardial ischemia reperfusion injury models, FDP group were made into myocardial ischemia reperfusion injury models and then were given FDP intervention, and FDP+AG490 group were made into myocardial ischemia reperfusion injury models and then were given FDP and JAK2 inhibitor AG490 intervention.Results: CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of I/R group were significantly higher than those of Sham group whereas Bcl-2, p-JAK2 and p-STAT3 protein expression in myocardial tissues were significantly lower than those of Sham group; CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of FDP group were significantly lower than those of I/R group whereas Bcl-2, p-JAK2 and p-STAT3 protein expression in myocardial tissue were significantly higher than those of I/R group; CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of FDP+AG490 group were significantly higher than those of FDP group whereas Bcl-2 protein expression in myocardial tissue was significantly lower than that of FDP group.Conclusion: FDP could reduce the myocardial ischemia reperfusion injury in rats by activating the JAK2/STAT3 pathway.     

R-wave amplitude responses to rapid atrial pacing: a marker for myocardial ischemia

Atrial pacing-induced changes in the sum of R-wave amplitude were measured in leads V5, X, Y, and Z at rates of 100 bpm (phase I), 150 bpm (phase II), and immediately after pacing (phase III) in 33 patients undergoing cardiac catheterization for evaluation of chest pain. Seventeen (51%) patients showed evidence of ischemia during atrial pacing (typical anginal pain and/or at least a 1 mm ST-segment depression) and 16 (49%) showed no evidence of ischemia. Mean R-wave amplitude changes from baseline in the ischemic patients were: phase I: -8% (p = not significant), phase II: +3% (p = not significant), and phase III: +13% (p less than 0.01); and in nonischemic patients: phase I: -11% (p less than 0.02), phase II: -18% (p less than 0.01), and phase III: +2% (p = not significant). These two distinct patterns of R-wave amplitude changes were highly sensitive (85%), specific (92%), and predictive (92%) for identifying patients with myocardial ischemia but did not correlate (p = not significant) with either the angiographically determined extent of coronary artery obstructive disease (CAD), resting left ventricular function, or the dynamic, atrial pacing-induced changes in left ventricular dimensions determined by M-mode and two-dimensional echocardiography. Thus, R-wave amplitude changes induced by atrial pacing can be used to identify patients with myocardial ischemia independent of coronary anatomy or resting left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fructose-1,6-Bisphosphate inhibits excess activation of Kupffer cell function induced by endotoxin

The effect and mechanism of action of fructose-1,6-bisphosphate (FBP) on Kupffer cell activation were studied in vitro. Kupffer cell was activated by isolation procedure alone from the hepatic tissue. In cultured rat Kupffer cells stimulated by endotoxin, treatment with 5–20 mM FBP not only preserved phagocytic activity, but also inhibited secretion of cytokines (tumor necrosis factor- and interleukin-1) and production of nitric oxide (NOx). Moreover, treatment with 10 mM FBP suppressed the elevation in the intracellular Ca²⁺ concentration on Kupffer cells stimulated by phorbol 12-myristate 13-acetate, which suggested that this effect may be one of the agents that limit the activation of Kupffer cells. The administration of FBP was effective in the prevention of endotoxin-induced hepatopathy, and we suggest that this may have useful clinical applications.     

Hemodynamic and electrocardiographic effects of fructose-1,6-diphosphate in acute myocardial infarction

Acute hemodynamic and electrocardiographic effects of fructose-1,6-diphosphate (FDP), an agent that is supposed to restore anaerobic glycolytic flux in the ischemic myocardium, were studied in 40 patients with acute myocardial infarction who were grouped into 4 subsets: subset 1, normal (15 mm Hg or less) pulmonary artery (PA) wedge pressure and normal (35 g-m/m2 or greater) left ventricular (LV) stroke work index; subset 2, elevated (more than 15 mm Hg) PA wedge pressure and normal LV stroke work index; subset 3, normal PA wedge pressure and reduced (less than 35 g-m/m2) LV stroke work index; subset 4, elevated PA wedge pressure and LV stroke work index moderately reduced to a range between 16 and 34 g-m/m2. Patients were randomized into an FDP (250 mg/kg body weight in isotonic saline solution intravenously in 20 minutes) and into a placebo group. Each subset contained 5 FDP- and 5 placebo-treated patients. After basal measurements, hemodynamic measurements were reassessed at 60, 90 and 120 minutes from the infusions, while a standard 12-lead electrocardiogram was recorded in the basal state and 120 minutes after infusion. Nonsignificant hemodynamic change was observed in the placebo subsets, and FDP failed to exert any effect in subsets 1, 2 and 3. A 24% (p less than 0.02) increase in cardiac index occurred 60 minutes after FDP in subset 4. LV stroke work index also increased, while PA wedge pressure remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrocardiographic correlates of myocardial ischaemia induced by atrial and ventricular pacing in dogs with coronary stenosis

We determined the electrocardiographic response to pacing-induced tachycardia in 45 dogs. Pacing was performed using left atrial, left atrial-right ventricular sequential or left atrial-left ventricular sequential modes at rates of 90 to 250 beats X min-1. Body surface isopotential maps in 15 dogs with normal coronary circulations defined the normal response to rate; surface potential extrema during the S-T segment increased in strength with increasing rate but spatial features remained constant. In the other 30 dogs, an ameroid constrictor was placed around the left circumflex coronary artery. Two weeks after implantation, atrial pacing to rates of 190 beats X min-1 or greater resulted in flat, S-T segment depression, with new and abnormal negative voltages registered over the inferior and left posterior torso. However, with either form of ventricular pacing, tachycardia with coronary obstruction did not alter the S-T segment response seen in control animals, in either intensity or spatial parameters. We interpret these findings to suggest that: in normal dogs, tachycardia produced a common electrocardiographic effect regardless of activation pattern; and tachycardia in the presence of coronary constriction results in subendocardial myocardial ischaemia that, with atrial pacing, reverses the normal transmural S-T segment potential gradient and causes body surface S-T segment depression, but with primary ventricular stimulation, the subendocardial ischaemia does not alter the transventricular repolarisation gradients sufficiently to generate body surface S-T segment shifts.     

快速起搏心房对犬心房电生理特性改变的研究

目的:研究心房颤动时心房肌的电生理改变。方法:快速持续起搏犬右心房24h制作房颤模型。比较起搏前(P0)、起搏后6h(P6)、12h(P12)和24h(P24)各时段的血压、心房传导速度和房颤波周长(atrial fibrillation cycle length,AFCL)的变化来分析心房肌的电生理改变。结果:起搏后平均动脉血压在P12[(126.06±7.01)mmHg]和P24时[(118.56±8.26)mmHg]较P0[(138.23±5.42)mmHg]明显下降。起搏24h后,P波时间是(78.91±6.21)ms,PA间期是(94±7.89)ms,与起搏前比较有显著延长(P<0.05)。连续快速起搏右心房在P6、P12和P24时的房颤自发维持的时间分别是5~10s、3~5min和15~20min。在起搏前和起搏后不同时间段,左房AFCL明显短于右房AFCL。右房房颤自发持续时间5~10s和15~20min的AFCL分别是(131.86±5.32)ms和(112.45±5.27)ms,P<0.05;左房房颤自发持续时间5~10s和15~20min的AFCL分别是(99.53±4.96)ms和(84...     

Ventricular fibrillation induced by transesophageal atrial pacing in hypertrophic cardiomyopathy

Sudden death is a rather frequent occurrence in patients withhypertrophic cardiomyopathy, yet the mechanism is uncertainin most cases. We describe a case of an 18 years old patientwith a family history of hypertrophic cardiomyopathy and suddendeath in whom ventricular fibrillation could be repeatedly inducedby means of transesophageal atrial stimulation with 1 : 1 AVconduction at a rate of 200 beats min^-1 and prevented by pharmacologicaldepression of AV node. The not particularly high ventricularrate at which VF occurred could suggest that in hypertrophiccardiomyopathy a major role in favouring VF induction is playedby the electro-physiological properties of the myocardium andthat sudden death can occur as a consequence of different atrialtachyarrhythmias.     

Ventricular fibrillation induced by transesophageal atrial pacing in hypertrophic cardiomyopathy

Sudden death is a rather frequent occurrence in patients withhypertrophic cardiomyopathy, yet the mechanism is uncertainin most cases. We describe a case of an 18 years old patientwith a family history of hypertrophic cardiomyopathy and suddendeath in whom ventricular fibrillation could be repeatedly inducedby means of transesophageal atrial stimulation with 1 : 1 AVconduction at a rate of 200 beats min^-1 and prevented by pharmacologicaldepression of AV node. The not particularly high ventricularrate at which VF occurred could suggest that in hypertrophiccardiomyopathy a major role in favouring VF induction is playedby the electro-physiological properties of the myocardium andthat sudden death can occur as a consequence of different atrialtachyarrhythmias.     

快速起搏心房对犬心房电生理特性改变的研究

目的:研究心房颤动时心房肌的电生理改变。方法:快速持续起搏犬右心房24h制作房颤模型。比较起搏前(P0)、起搏后6h(P6)、12h(P12)和24h(P24)各时段的血压、心房传导速度和房颤波周长(atrial fibrillation cycle length,AFCL)的变化来分析心房肌的电生理改变。结果:起搏后平均动脉血压在P12[(126.06±7.01)mmHg]和P24时[(118.56±8.26)mmHg]较P0[(138.23±5.42)mmHg]明显下降。起搏24h后,P波时间是(78.91±6.21)ms,PA间期是(94±7.89)ms,与起搏前比较有显著延长(P<0.05)。连续快速起搏右心房在P6、P12和P24时的房颤自发维持的时间分别是5~10s、3~5min和15~20min。在起搏前和起搏后不同时间段,左房AFCL明显短于右房AFCL。右房房颤自发持续时间5~10s和15~20min的AFCL分别是(131.86±5.32)ms和(112.45±5.27)ms,P<0.05;左房房颤自发持续时间5~10s和15~20min的AFCL分别是(99.53±4.96)ms和(84.31±2.84)ms,P<0.05。结论:快速心房起搏建立的房颤模型可引起血压进行性下降、心房传导速度减慢和AFCL缩短。     

心房颤动犬心房肌肾素-血管紧张素系统改变

目的探讨慢性心房快速起搏诱发心房颤动(房颤)犬心房肌肾素血管紧张素系统(RAS)的改变。方法13只犬随机分为假手术组(n=6)和起搏组(n=7)。起搏组犬无菌开胸后在右心房缝植5对心外膜记录电极,电极尾端经皮下由犬背部穿出;在右心耳缝植螺旋型起搏电极,连接实验用AOO高频起搏器(400次/min),心房快速起搏6周,建立房颤犬模型;假手术组犬仅缝植心外膜记录电极和起搏电极而不起搏。经心外膜电极记录各组犬房颤诱发情况;采用放射免疫方法检测两组犬左心房及右心房组织血管紧张素Ⅰ(AngⅠ)、血管紧张素Ⅱ(AngⅡ)含量及肾素活性;采用逆转录聚合酶链反应(RTPCR)检测两组犬心房肌肾素、血管紧张素原和血管紧张素转换酶mRNA表达水平改变。结果(1)起搏组7只犬均经短阵快速刺激(burstpacing)诱发出房颤,房颤诱发率和平均持续时间较假手术组显著增加(P<0.01);(2)起搏组犬心房肌AngⅠ、AngⅡ含量较假手术组犬心房肌明显升高(P<0.01),肾素活性亦显著增加(P<0.01);同一组犬左心房与右心房组织AngⅠ、AngⅡ含量及肾素活性差异无统计学意义(P>0.05);(3)起搏组犬心房肌肾素、血管紧张素原和血管紧张素转换酶mRNA表达较假手术组犬心房肌显著上调(P<0.01)。结论慢性心房快速起搏诱发房颤犬心房肌AngⅠ、AngⅡ含量及肾素活性显著增加,可能是局部RAS基因表达上调的结果,提示房颤伴随心房肌RAS激活。