Outcomes of the patients of heart failure with reduced ejection fraction receiving inotropic support in initial 6 hours: Insights from Manipal Heart Failure Registry

Heart failure (HF) is responsible for 1.8 million admissions annually in India with an additional burden of mortalityand re-hospitalizations. Positive inotropes with multiple mechanisms, such as dopamine and levosimendan, are beingused for more than three decades to treat the patients of acute HF with reduced ejection fraction (HFrEF). This studycompared the outcomes of the dopamine and the levosimendan up to 180 days. We have selected the patients fromManipal Heart Failure Registry who were diagnosed to have HFrEF (left ventricular EF less than 50%) and wereinitiated on either dopamine or levosimendan in first 6 hours of hospitalization. The study included a total of 187patients; among them, 120 patients were analyzed in the dopamine group, and 67 patients in the levosimendan group.Dopamine was initiated as intravenous infusion with the dose of 2.5 microgram/kilogram/minute (mcg/kg/minute)and up-titrated up to 10 mcg/kg/minute. Levosimendan was also administered intravenously with a dose of 0.1 mcg/kg/minute and up-titrated up to 0.4 mcg/kg/minute. The primary outcomes include a composite of all-cause mortalityand re-hospitalization at 30-days and 180-days follow-ups. The in-hospital mortality, 30-days mortality and 180-daysmortality, and composite outcomes were noted higher in levosimendan treated patients even after matched demographicparameters (age and gender) and comparable comorbidities and risk factors, i.e., smoking, alcohol consumption,hypertension, diabetes mellitus, and atrial fibrillation. However, reduced EF, raised serum creatinine, procalcitonin,and N-terminal pro b-type natriuretic peptide levels and high use of digoxin were noticed in levosimendan groupduring the initial period of index-hospitalization and these can be considered as confounding factors for future studies.

Aspectos novedosos de la intoxicación digitálica / New aspects on digitalis toxicity

Los digitálicos son fármacos con capacidad de aumentar la contractilidad miocárdica (inotrópico positivo), que han desempeñado un rol primordial en el tratamiento de pacientes con insuficiencia cardiaca; su uso inapropiado puede traer complicaciones serias a estos pacientes, incluso, hasta la muerte. La más importante de estas complicaciones es la intoxicación digitálica, originada por la sobredosis de dichos fármacos, a causa de la combinación del efecto inhibitorio en la conducción nodal y la estimulación sobre las fibras individuales auriculares y ventriculares. Debido al uso frecuente de estos medicamentos en todos los niveles de atención de salud y lo difícil que resulta diagnosticar dicha complicación por la complejidad de su cuadro clínico y de su expresión electrocardiográfica, se realizó una revisión bibliográfica exhaustiva sobre el tema para brindar amplia información, que permita una atención adecuada a los pacientes con este diagnóstico

Digitalis are drugs with the capacity of increasing myocardial contractility (inotropic positive agents) which have carried out an important role in the treatment of heart failure; their inappropriate use can bring severe complications to the patient, even, to death. The most important in these complications is the digitalis toxicity, originated by the overdose of these drugs, caused by the combination of the inhibitory effect in the nodal conduction and stimulation on the individual atrial and ventricular fibers. Due to the frequent use of these medications at all levels of medical care and to the difficulty in diagnosing this complication caused by the complexity of their clinical pattern and of their electrocardiographic expression, an exhaustive literature review was carried out on the topic to give a wide information that allows an appropriate care to the patients with this diagnosis

Effects of Ethyl Acetate Part from Ethanol Extract of Miao Medicine Periploca forrestii on Cardiac Function of Isolated Frog Heart / 中国药房

OBJECTIVE： To study the effects of ethyl acetate part form the ethanol extract of Periploca forrestii on cardiac function of isolated frog heart， and to primarily investigate its potential mechanism. METHODS： The isolated frog heart samples were prepared by using the intube method of steinmann. The Ren’s solution （blank control）， 1.70 mg/mL and 3.48 mg/mL ethyl acetate part from ethanol extract of P. forrestii were used to perfuse the sample. The BL-420 biological function experimental system was used to record the changes in heart rate and myocardial contractility. The effects of ethyl acetate part from ethanol extract of P. forrestii on cardiac function of isolated frog heart were investigated. After perfused with 10 mg/L atropine， 20 μL isoproterenol， 1 μL low calcium （per 1 000 mL pure water contain 0.06 g CaCl2）， high calcium Ren’s solution （per 1 000 mL pure water contain 0.24 g CaCl2）， adding 1.74 mg/mL ethyl acetate part from ethanol extract of P. forrestii， the changes of myocardial contractility in isolated hearts were recorded by BL-420 biological function experimental system. Myocardial tissue was collected after perfused with Ren’s solution （blank control） and ethyl acetate part from ethanol extract of P. forrestii with 1.74 and 3.48   mg/mL. The activity of Na+-K+-ATPase， Ca2+-Mg2+-ATPase and AChE were detected to investigate the potential mechanism of the effects of ethyl acetate extract from ethanol extract of P. forrestii on cardiac function. RESULTS： Compared with blank control， mean myocardial contractility was significantly decreased （P＜0.001） after adding 1.74， 3.48 mg/mL ethyl acetate part form ethanol extract of P. forrestii， but had no significant on heart rate （P＞0.05）. With the increase of extracellular Ca2+ concentration， the inhibitory effect of ethyl acetate part from ethanol extract of P. forrestii on isolated frog heart contraction also increased gradually. After adding atropine and isoproterenol， the inhibitory effect of the ethyl acetate part form ethanol extract of P. forrestii on isolated frog heart contraction decreased to some certain. The activity of Na+-K+-ATPase in cardiac tissue was not significantly changed （P＞0.05）， the activity of Ca2+-Mg2+-ATPase was significantly increased （P＜0.05）， and the activity of AChE was significantly decreased （P＜0.05） after perfused with 1.74， 3.48 mg/mL ethyl acetate part form ethanol extract of P. forrestii. CONCLUSIONS： The ethyl acetate part from the ethanol extract of P. forrestii can inhibit the contractile activity of the isolated frog heart and has a certain negative inotropic effect. The mechanism may be related to the increase of Ca2+-Mg2+-ATPase activity， inhibition of AChE activity， blocking of calcium channel in the cell membrane， the activation of M receptor and blocking of β receptor.

Influence of tea pigment on cardiac activity in exsomatized toads of myocardial ischemia / 重庆医学

Objective To observe the influence of tea pigment on myocardial contractility,electrocardiogram(ECG) and heart rate in exsomatized toads under the condition of myocardialischemia.Methods Sixty toads were divided into the normal exsomatized toad heart group(A) and myocardial ischemia toad heart(B).Then the group A was re-divided into the Ringer's solution group (A1),tea pigment low dose(200 mg/L) group(A2) and the high dose(400 mg/L) group(A3);the group B was re-divided into the pituitrin model group(B1),pituitrin + tea pigment low dose(200 mg/L) group(B2) and high dose(400 mg/L) group(B3).The BL-420S biological function experiment system was used to record the myocardial contractile force and ECG change curve of exsomatized toad.Results Compared with the group A1,the myocardial contractility in the group A3 was obviously increased(P＜0.05),the difference in the group A2 had no statistical significance(P＞0.05);the QRS peak value of ECG and heart rate had no statistically significant difference(P＞0.05);compared with the group A1,the myocardial contractility,ECG QRS peak value and heart rate in the group B1 were significantly decreased(P＜0.05);compared with the group B1,the myocardial contractility,ECG QRS peak value and heart rate in the group B2 and B3 were significantly increased(P＜0.05).Conclusion Tea pigment can obviously improve the decrease of the exsomatized toad cardiac activity caused by myocardial ischemia.

Role of myosin regulatory light chain phosphorylation in the pathogenesis of chronic heart failure / 上海交通大学学报（医学版）

In the embryonic period, myosin regulatory light chain (MYL2) plays a pivotal role in the development and function of the heart. A large number of studies have previously confirmed that the mutation of MYL2 gene, also known as MLC2, confers intimate associations with hypertrophic cardiomyopathy. MYL2 gene mutation impacts the structure and function of myosin, thereby leading to the occurrence and progression of hypertrophic and dilated cardiomyopathy as well as the following chronic heart failure. Importantly, MYL2 phosphorylation renders crucial effects in the processes of cardiac contraction, ventricular torsion and cardiac function.

Acute exposure to lead increases myocardial contractility independent of hypertension development

We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetate iv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na+,K+-ATPase and myosin Ca2+-ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2 vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13 vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na+,K+-ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension.

Myocardial Contractility, Perfusion, and Viability Analysis Using Multidetector CT in Patients with Ischemic Heart Disease

The imaging technique that can provide detailed information on the left ventricular function, myocardial perfusion and viability at the same time will not only be helpful for the prognostic assessment of patients with ischemic heart disease but also be valuable in choosing appropriate therapeutic strategies. In recent years, multidetector CT (MDCT) has been proposed as a useful non-invasive imaging method of evaluating both coronary artery stenoses and cardiac morphology at the same time. MDCT has proved to be in excellent agreement with echocardiography and magnetic resonance imaging in the assessment of the left ventricular function. In addition, MDCT can provide information on myocardial viability, which can be assessed from the left ventricular wall thickness, myocardial perfusion, and a delayed contrast enhancement pattern. Despite several shortcomings to be the first-line modality for the assessment of ischemic heart disease, MDCT can provide valuable additional dynamic information in patients undergoing MDCT coronary angiography.

Direct Myocardial Depressant Effect of Desflurane: Mechanical and Electrophysiological Actions in Vitro / 대한마취과학회지

BACKGROUND: Desflurane actions on myocardial contractility and cellular electrophysiologic behavior were studied in isolated guinea pig and rat right ventricular papillary muscles. METHODS: The isometric force of isolated guinea pig ventricular papillary muscles was studied in normal and 26 mM K+ Tyrode's solution at various stimulation rates. Experiments using rat papillary muscles under normal Tyrode's solution at the rested-state (RS) and using guinea pig papillary muscles under low Na+ Tyrode's solution (25 mM) were performed to evaluate the effect of Ca2+ release from the sarcoplasmic reticulum (SR). Effects of desflurane on SR function in situ were examined by its effect on rapid cooling contractures (RCCs). Normal and slow action potentials (APs) were evaluated by using a conventional microelectrode technique. Finally, Ca2+ currents of isolated guinea pig ventricular myocytes were examined using the whole cell patch clamp technique. RESULTS: 1 MAC (minimum alveolar concentration: 6%) and 2 MAC desflurane were applied. 1 MAC and 2 MAC desflurane depressed guinea pig myocardial contractions by ~30% and ~60%, respectively, from RS to 3 Hz stimulation rates. 1 MAC (1.15%) and 2 MAC isoflurane depressed peak force by ~25% and ~45%, respectively. Contractile force after rest in rat and guinea pig myocardium under low Na+ Tyrode's solution showed modest depression. In the partially depolarized, adrenergically stimulated myocardium, 1 MAC and 2 MAC desflurane caused a marked depression of the late peak force (1 MAC:~60%, 2 MAC:~80%) with moderate changes of the early peak force (1 MAC: ~20%, 2 MAC: ~40%). RCCs were abolished at 1 MAC desflurane. Desflurane did not alter the peak amplitude or maximum depolarization rate of normal and slow APs, however, AP duration was significantly prolonged. In isolated guinea pig myocytes at room temperature, 1 MAC and 2 MAC desflurane caused a ~28% and ~55% decrease in Ca2+ currents, respectively. CONCLUSIONS: These results indicate that desflurane causes a dose-dependent depression of contractile force in isolated myocardium, which is comparable to that of isoflurane. The depression seems to be related, at least in part, to its ability to reduce inward Ca2+ currents through the cardiac membrane. Therefore, it is likely that various methods employed to enhance inward Ca2+ current may improve the hemodynamic depression induced by desflurane.

Gated Myocardial SPECT

The advent of gated myocardial SPECT has achieved onestop imaging in coronary artery diseases. Perfusion at rest and stress is measured and quantified using software. Myocardial contractility can be determined by quantifying the global function or regional contractility markers such as wall motion or systolic thickening. Excellent reproducibility was shown for ejection fraction and left ventricular volumes and mass. Improvement of the ejection fraction by 5% or a decrease of volumes by 10 ml can be used as criteria on a postoperative or followup scan. To achieve postoperative global improvements, an increase of systolic thickening > 15% of regional segments is needed. Even the prolonged transient stunning can be detected on gated myocardial SPECT as one gated SPECT indicates the perfusion and corn tractility of each segment. Lowdose dobutaminechallenged gated SPECT is feasible and is believed to parallel lowdose dobutamine echocardiography for determination of myocardial viability. Gated SPECT was also helpful to differentiate artifacts and for risk stratification of diabetic patients ; normal perfusion with abnormal function means a worse prognosis. Gated myocardial SPECT is mandatory if SPECT cameras have the capability of gating because it provides clinicians with information not only on diagnosis but also on prognosis, treatment strategy and risk stratification.

Left Ventricular Systolic Function Indexes by Echocardiography in Hypertensive Subjects

BACKGROUND: The evaluation of cardiac performance is very important to management and prognostication in hypertensive patients. Although ejection phase indexes have been used for assessing left ventricular systolic function they are highly dependent on cardiac loading conditions. In addition, these load-dependent indexes may not differentiate accurately between the effects of altered loading canditions and intrinsic abnormalities in contractile function of cardiac muscle. In recent years, the end-systolic pressure to volume of dimension relations have emerged as a reliable measure of the myocardial contractility. The authors studied the changes of end-systolic pressure to volume or dimension relations according to pre-load and after-load by using the Echocardiogram. METHODS: By 2-D and M-mode Echocardiogram we measured the ratio of end-systolic wall stress to end-systolic volume index(EWS/ESVI), peak systolic pressure or end-systolic dimension of left ventricle(PSP/ESD), peak systolic pressure to end-systolic volume index(PSP/ESVI) to assess myocardial contractility in 139 normal subjects and 55 patients with untreated essential hypertension. Then we compare these indexes to systemic blood pressure & left ventriclular end-diasolic dimension. RESULTS: 1) EF, %FS, and mVcf were similar in both groups, but PSP/ESD, PSP/ESVI, EWS/ESVI for the hypertensive group were greater than that for the normal group. 2) There was poor relation between arterial blood pressure and EWS/ESVI than oter load independent indexes in both groups. 3) There was poor reation between left ventricle end diastolic dimension than oter load independent indexes in both groups. CONCLUSION: The ratio of end-systolic wall stress to end-systolic volume index(EWS/ESVI) is a relible load independent index to assess myocardial contractility in hypertension.

Effect of Intracoronary Nicardipine on Functional Recovery of Stunned Myocardium in Halothane-Anesthetized Dogs / 대한마취과학회지

BACKGROUND: Myocardial calcium overload during reperfusion may contribute to myocardial stunning. The protective effect of nicardipine against post-ischemic myocardial dysfunction was investigated. METHODS: Twenty-two halothane-anesthetized dogs were subjected to 15 minutes of left anterior descending coronary artery (LAD) occlusion and subsequent 3 hour reperfusion. One group of dogs (n=11) received nicardipine (1 microgram/kg/min) and another group (n=11) received saline (0.5 ml/kg/h) through intracoronary catheter for 1 hour beginning 15 minutes before LAD occlusion. Systolic shortening (%SS) and preload recruitable stroke work slope (Mw), as an index of regional myocardial contractility, and IMP-tau (time constant of myocardial relaxation based on intramyocardial pressure (IMP)) and post-systolic shortening (%PSS), as an index of regional diastolic function, were evaluated. LAD blood flow was measured by Doppler flowmeters as well. RESULTS: Regional systolic as well as diastolic functions during acute myocardial ischemia were similar between the two groups. However, Mw recovered to the baseline value with the onset of reperfusion in the nicardipine group but was significantly decreased throughout the reperfusion period in the controls. After 3 hours of reperfusion, the nicardipine group had recovered 67% of %SS, compared with 20% of the control group. IMP-tau was restored to the baseline value by 60 min of reperfusion in the control group but was significantly prolonged in the nicardipine group throughout the reperfusion period. CONCLUSIONS: Intracoronary nicardipine enhances the recovery of regional contractile function but prolongs myocardial relaxation in the canine model of myocardial stunning.

Effect of High-dose Fentanyl Versus Propofol-Fentanyl Anesthesia on Functional Recovery of Stunned Myocardium in Dogs / 대한마취과학회지

BACKGROUND: The purpose of this study was to evaluate the effects of propofol-fentanyl anesthesia in comparison with fentanyl alone on the functional recovery of postischemic reperfused myocardium and on the incidence of ischemia-reperfusion arrhythmia in an open-chest canine model. METHODS: Dogs were subjected to 15 minutes of left anterior descending coronary artery (LAD) occlusion followed by 3 hour of reperfusion during fentanyl (n=12) or propofol plus fentanyl (n=11) anesthesia. Regional myocardial contractility was evaluated using systolic shortening (%SS), the preload recruitable stroke work slope (Mw), intramyocardial pressure (IMPs), and regional stroke work area (RSWA). RESULTS: Dogs anesthetized with propofol-fentanyl had a significantly lower regional (%SS, Mw, IMPs, and RSWA) and global myocardial contractility (cardiac index, mean aortic pressure and left ventricular dP/dt) than fentanyl anesthetized dogs during pre-occlusion baseline. LAD occlusion produced a significant reduction in the regional contractile functions (%SS, Mw, IMPs, and RSWA) in both groups. During reperfusion, gradual return of the regional contractile functions (%SS, Mw, IMPs, RSWA) toward their respective baselines were observed without any differences between the groups. However, ventricular fibrillation associated with LAD occlusion was lower in the propofol-fentanyl group than in the fentanyl group (zero vs 33%, p<0.05). CONCLUSIONS: Propofol supplementation over moderate-dose fentanyl reduces reperfusion arrhythmia during coronary occlusion and subsequent reperfusion but does not improve functional recovery of post-ischemic, reperfused myocardium compared with high-dose fentanyl anesthesia in dogs.

The effects of propofol on myocardial contractility in rat vivo / 中华麻醉学杂志

To determine the effect of propofol on myocardial contractility. Method: Twenty hamsters were allocated to receiving intravenous propofol 2.5mg?kg~(-1)(group Ⅰ) or thiopentone 4mg?kg~(-1)as control (group Ⅱ) dp/dt_(max), was determined using a catheter inserted into the left ventricle from right carotid artery. LVP (LVSP, LVDP, LVMP), CVP, HR were recorded simutaneously. Resutt: dp/dt_(max), decreased insignitieantly in group Ⅰ but signitieantly in group Ⅱ. LVP(LVSP, LVDP, LVMP) decreased, while CVP increased significantly in both groups (P0.05). Conclusion.. The influence of propofol on myocardial contractility is weaker than that of thiopenone.

Beneficial effects of nitrendipine on diabetic cardiomyopaty in rats / 中国糖尿病杂志

The effects of nitrendipine (Nit) on myocardial contractility, myocardial succinate de-hydrogenase (SDH) and cytochrome oxidase (CCO) activities in streptozotocin (65mg/kg) diabetic rats were studied. Four weeks after the induction of diabetes, the rats were treated with Nit (30mg ?kg -2/day) for 4 weeks. The results showed that ventricular diastolic function was affected after 4 weeks of diabetes, and both ventricular diastolic and systolic functions were obviously involved after 8 weeks. These changes were significantly improved in diabetic rats receiving Nit treatment. The myocardial SDH and CCO activities in diabetic animals were markedly lower as compared to controls. The attenuation of these enzyme activities in diabetic rats was significantly reversed by administration of Nit. These findings suggest that Nit treatment may exhibit some beneficial effects on diabetic cardiomyopathy.

Effect of Burn Injury on the Contractile and Relaxation function of Isolated Perfusion Heart in Guinea-pigs / 第三军医大学学报

By mean of the isolated perfused working heart model, the changes of myocardial contractile and relaxation functions, ventricular cell action potentials, myocardial oxygen and glucose consumptions etc. were observed at 1st,3rd, 8th and 24th h after burn injury in the guinea-pigs inflictedly III degree burn injury on 35% TBA. The results indicate that. 1 ) The contractile and relaxation functions go through a time course of 'normal-decrease-recover', i.e. the cardiac functions show a normal level within 1 h after burn injury. Then they are depressed gradually,and to the lowest at 8th h or so, after burn injury. The cardiac functions recover partly at 24th h after burn injury. It suggests that there is a repaired mechanism by itself in heart of the burn animal; 2 ) The depression of myocardial contractile and relaxation functions are related with depression of the oxygen consumption rather than reduce of intaking in nutrients; 3) the influencing factors of burn injury on the coronary flow and electrical activity of myocardial cells could be removed easily by the perfusate. It shows that these effects may be result from the extracardiac neurohumoral factors.