Ureterovesical junction obstruction causes increment in smooth muscle contractility,and cholinergic and adrenergic activity in distal ureter of rabbits

Background/Purpose

The controversy in management of primary obstructed megaureter necessitates further elucidation of the underlying pathophysiology. We evaluated smooth muscle contractility, and cholinergic, adrenergic and serotonergic activity of rabbit distal ureters after ureterovesical junction (UVJ) obstruction.

Methods

Sham (SH) operation, partial obstruction (PO) and complete obstruction (CO) of the right UVJ were performed in rabbits. Three weeks later, distal ureters were isolated; spontaneous contractions (SC), contractile responses to electrical field stimulation (EFS), high KCl, carbachol, phenylephrine and serotonin were recorded.

Results

SC amplitudes increased in CO compared to PO and SH (p < 0.001). SC frequency was higher in CO (p < 0.05). EFS-induced contraction amplitudes were greater in CO than other groups (p < 0.05). High KCl-induced contractions were greater in CO (p < 0.001) and PO (p < 0.01). Carbachol-induced contractility was enhanced in CO and PO (p < 0.05). Contractile response to phenylephrine was greater in CO than other groups (p < 0.05). Serotonin induced contractile responses in CO and PO, greater in CO (p < 0.05). UVJ obstruction also increased spontaneous contractility in contralateral PO and CO ureters.

Conclusions

UVJ obstruction increased spontaneous and neurotransmitter-induced contractions in an obstruction grade-dependent manner. Obstruction also altered contractility of the contralateral ureters. Our findings may serve to provide further understanding of the pathophysiology of megaureter.     

Suppressed phospholamban levels differentiate irreversibly dysfunctional from hibernating myocardium in humans

Objectives We studied whether dysfunction of human hibernating (HIB) and irreversibly dysfunctional myocardium (IRDM) are associated with altered levels of the sarcoplasmatic reticulum calcium handling proteins Ca²⁺-ATPase (SERCA2a) and its inhibitor phospholamban (PLB).

Design In 12 patients myocardial biopsies were taken during bypass surgery and analysed for contents of these proteins. We classified regions as control, HIB, or IRDM based on echocardiographic studies before and 6 months after surgery.

Results SERCA2a content (mean±SEM) was similar to control in HIB and IRDM (2.6±1.7, 3.8±2.0, and 3.4±1.9 units/g non-collagen protein (NCP), p=0.40). PLB content was similar to control in HIB (2.6±0.4 and 3.5±0.5 units/μg NCP) but reduced in IRDM (0.9±0.2 units/μg NCP, p<0.05). SERCA2a:PLB ratio, an indicator of SERCA2a activity, did not differ between control and HIB (1.2±0.3 and 1.4±0.4 units/μg NCP) but was increased in IRDM (5.1±1.7 units/μg NCP, p<0.05).

Conclusions Inappropriate SERCA2a activity due to suppressed PLB levels may represent a maladaptive mechanism in chronic ischemic myocardium being causally linked to irreversibility of left ventricular dysfunction.     

Effect of preconditioning temperature on cardioprotection during global ischemia-reperfusion in the rat heart

BACKGROUND: Myocardial ischemic preconditioning (PC) is a protective intervention that aims to reduce the deleterious effects of ischemia-reperfusion injury. OBJECTIVES: : To assess the comparative efficacy of ischemic PC induced at hypothermic, normothermic and hyperthermic temperatures on the postischemic recovery of left ventricular contractile and coronary vascular functions in the aortic perfused rat heart model. METHODS: An isolated aorta-perfused (Langendorff) rat heart model was used. Hearts were studied in eight different groups (n=5 each). Unprotected ischemia for 60 min served as control. For the remaining seven groups, ischemia was preceded by PC at 10 degrees C, 20 degrees C, 30 degrees C, 34 degrees C, 37 degrees C, 40 degrees C and 42 degrees C achieved by two episodes of 5 min ischemia at the designated PC temperature and 10 min of reperfusion, respectively. The postischemic recovery in contractile (maximum developed pressure and left ventricular end-diastolic pressure) and coronary vascular functions (coronary flow and coronary vascular resistance) was assessed at the end of 30 min reperfusion. RESULTS: Hyperthermic PC provided optimal preservation and resulted in a 25% increase in the myocardial and 15% increase in the coronary vascular tolerance to ischemia. Normothermic PC resulted in a 21% increase in myocardial and 14% increase in coronary vascular tolerance to ischemia. Hypothermic PC was comparatively less effective and resulted in 11% increase in myocardial and 15% increase in the coronary vascular tolerance to ischemia. The temperature-dependence of PC may be summarized as: PC-42 degrees C > PC-40 degrees C > PC-37 degrees C > PC-34 degrees C > PC-30 degrees C > PC-20 degrees C > PC-10 degrees C. CONCLUSIONS: The results of the present study indicate that the extent of reversibility of the ischemic damage depends on the PC temperature and that optimal preservation occurred at the ideal PC temperature between 40 degrees C and 42 degrees C.     

微血管周细胞收缩功能的研究进展

周细胞定位在微血管壁外侧,是微血管的重要组成细胞之一,它在微血管的形成及局部血流调节中发挥重要作用。周细胞是类似平滑肌细胞的一类细胞,表达多种收缩蛋白,具有收缩性。周细胞收缩可调节微血管管径及血流,控制局部微血流的灌流量。近年,越来越多的研究表明周细胞的收缩功能与多种微血管疾病的病变过程有关,因此日益受到关注。对其收缩功能的进一步理解,可能为治疗微血管疾病提供新的方法。     

Pharmacological inhibition of βIIPKC is cardioprotective in late-stage hypertrophy

We previously found that in the hearts of hypertensive Dahl salt-sensitive rats, βIIPKC levels increase during the transition from compensated cardiac hypertrophy to cardiac dysfunction. Here we showed that a six-week treatment of these hypertensive rats with a βIIPKC-specific inhibitor, βIIV5-3, prolonged their survival by at least 6 weeks, suppressed myocardial fibrosis and inflammation, and delayed the transition from compensated hypertrophy to cardiac dysfunction. In addition, changes in the levels of the Ca²⁺-handling proteins, SERCA2 and the Na⁺/Ca²⁺ exchanger, as well as troponin I phosphorylation, seen in the control-treated hypertensive rats were not observed in the βΙΙPKC-treated rats, suggesting that βΙΙPKC contributes to the regulation of calcium levels in the myocardium. In contrast, treatment with the selective inhibitor of βIPKC, an alternative spliced form of βIIPKC, had no beneficial effects in these rats. We also found that βIIV5-3, but not βIV5-3, improved calcium handling in isolated rat cardiomyocytes and enhanced contractility in isolated rat hearts. In conclusion, our data using an in vivo model of cardiac dysfunction (late-phase hypertrophy), suggest that βIIPKC contributes to the pathology associated with heart failure and thus an inhibitor of βIIPKC may be a potential treatment for this disease.     

Functional effects of the DCM mutant Gly159Asp Troponin C in skinned muscle fibres

We recently reported a dilated cardiomyopathy (DCM) causing mutation in a novel disease gene, TNNC1, which encodes cardiac troponin C (TnC). We have determined how this mutation, Gly159Asp, affects contractile regulation when incorporated into muscle fibres. Endogenous troponin in rabbit skinned psoas fibres was partially replaced by recombinant human cardiac troponin containing either wild-type or Gly159Asp TnC. We measured both the force–pCa relationship of these fibres and the activation rate using the caged-Ca²⁺ compound nitrophenyl-EGTA. Gly159Asp TnC had no significant effect on either the Ca²⁺ sensitivity or cooperativity of force generation when compared to wild type. However, the mutation caused a highly significant (ca. 50%) decrease in the rate of activation. This study shows that whilst not affecting the force–pCa relationship, the mutation Gly159Asp causes a significant decrease in the rate of force production and a change in the relationship between the rate of force production and generated force. In vivo, this mutation may cause both a slowing of force generation and reduction in total systolic force. This represents a novel mechanism by which a cardiomyopathy-causing mutation can affect contractility.     

产后盆底功能障碍性疾病与盆底肌收缩力及其相关因素分析

目的:探讨产后盆底功能障碍性疾病(PFD)与盆底肌收缩力的关系及其相关因素。方法:选择产后42~60天有产后尿失禁(UI)或盆腔器官脱垂(POP)的妇女为研究组(102例),其中UI患者66例(UI组),POP患者36例(POP组);另选择同期产后复查的正常产妇100例为对照组。对研究组和对照组的一般情况进行问卷调查,并采用肌电图描记法对UI组、POP组和对照组的盆底肌力进行评估。结果:1研究组的年龄、分娩前体重指数(BMI)、新生儿体重、阴道分娩率及有腹压增高史率明显高于对照组(P0.05;P0.01)。2研究组肌电图持续收缩值和快速收缩值均明显低于对照组(P0.01)。3研究组中UI组的快速收缩值明显低于POP组和对照组(P0.01),研究组中POP组的持续收缩值明显低于UI组和对照组(P0.01)。结论:产后PFD的发生可能与年龄、分娩前BMI、新生儿体重、阴道分娩等因素有关;产后PFD与盆底肌收缩力下降有关,其中POP可能与Ⅰ类肌力下降有关,而UI可能与Ⅱ类肌力下降有关。     

Assessment of Ventricular Contractility During Cardiac Magnetic Resonance Imaging Examinations Using Normalized Maximal Ventricular Power

Normalized maximal ventricular power (nPWR^max) is an index of cardiac function which measures the innate blood pumping ability, or contractility, of the left ventricle (LV), and its noninvasive assessment could prove useful in a variety of patients. nPWR^max is defined as the maximum instantaneous product of LV pressure and the rate of change of LV volume, divided by the end diastolic volume squared. We have quantified nPWR^maxnoninvasively in humans by pairing magnetic resonance imaging (MRI) LV volume measurements with aortic pressure estimated using radial artery tonometry and a frequency domain transfer function. In healthy volunteers undergoing cardiac MRI we have tested the sensitivity of nPWR^max to LV contractility with dobutamine and to cardiac loading with methoxamine, a vasoconstrictor. We have found that aortic pressures can be reliably estimated using a transfer function, which we generated and validated in a group of patients undergoing cardiac catheterization. Furthermore, we found that nPWR^max was unchanged by methoxamine, yet sensitive to contractility, with a 325% increase at dobutamine levels half that given during routine clinical cardiac stress tests for ischemia. In conclusion, we have shown that ventricular contractility can be assessed independent of cardiac loading in patients during routine noninvasive cardiac imaging examinations. © 2001 Biomedical Engineering Society. PAC01: 8761Pk, 8719Hh, 8719Uv