The aim of this study was to explore the effects of cholecystokinin octapeptide (CCK-8) on cardiac function and the receptor mechanism in anesthetized rats. The mean arterial pressure (MAP), heart rate (HR), the left ventricle systolic pressure (LVP) and the maximal/minimum rate of LVP (+/-LV dp/dt(max)) were measured. The results obtained are as follows. (1) Low dose of CCK-8 (0. 4 microgram/kg i.v.) caused tachycardia and slight increase in MAP, LVP and LV dp/dt(max) (P<0.01), while medium dose (4.0 microgram/kg i.v.) and high dose of CCK-8 (40 microgram/kg i.v.) elicited a bradycardia and marked increase in MAP, LVP and LV dp/dtmax (P<0.01). (2) Proglumide (1.0 mg/kg i.v.), a CCK-receptor (CCK-R) antagonist, significantly inhibited the pressor effects of CCK-8, whilst it reversed the bradycardic responses (P<0.01). (3) Using reverse transcription polymerase chain reaction (RT-PCR), CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR) mRNA were expressed in myocardium of rats. The above results indicate that CCK-8 may enhance cardiac function in a dose-dependent manner and elicit a change in HR, which is likely induced by the activation of CCK-R on myocardium.
Animals ; Dose-Response Relationship, Drug ; Heart Rate ; drug effects ; Male ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Cholecystokinin ; drug effects ; Sincalide ; administration & dosage ; pharmacology ; Ventricular Function, Left ; drug effects ; Ventricular Pressure ; drug effects

The aim of this article was to investigate the dependence of ventricular wallstress-induced refractoriness changes on pacing cycle lengths and its mechanism in anaesthetized rabbits. The rabbit heart preparation was used. The left ventricular afterload was increased by partially clipping the root of the ascending aorta. The changes in effective refractory periods (ERP) induced by the left ventricular afterload rising were examined at different pacing cycle lengths (1000, 500, 300 and 200 ms). In addition, the effect of streptomycin on these changes was also observed. The results are as follows: (1) The rising of left ventricular afterload led to marked changes in ERP at rapidly pacing cycle lengths (300 ms, 21+/-5 ms, 17.0%; 200 ms, 19+/-3 ms, 18.8%. P<0.01) than at slow ones (1000 ms, 3+/-2 ms, 1.5%; 500 ms, 7+/-3 ms, 4.0%. P>0.05); (2) Streptomycin inhibited the changes caused by the left ventricular afterload rising at pacing cycle lengths 300 ms and 200 ms (P>0.05). It is suggested that ventricular wallstress-induced refractoriness changes are pacing cycle length-dependent, and the effect of streptomycin appears to be consistent with the inhibition of stretch-activated ion channels.
Animals ; Aorta ; Cardiac Pacing, Artificial ; Constriction ; Mechanoreceptors ; drug effects ; physiology ; Rabbits ; Refractory Period, Electrophysiological ; drug effects ; Streptomycin ; pharmacology ; Ventricular Function ; drug effects ; physiology

To systematically evaluate the clinical efficacy and safety of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in the treatment of hypertensive left ventricular hypertrophy. China National Knowledge Infrastructure(CNKI), Wanfang, VIP, PubMed, EMbase, Cochrane Library, Ovid and Web of Science databases were searched by computer to retrieve the randomized controlled trials(RCTs) of Compound Danshen Dripping Pills combined with conventional antihypertensive drugs in the treatment of hypertensive left ventricular hypertrophy from the establishment of databases to July 2020. After two researchers performed data retrieval, data extraction, and risk assessment of bias, they used RevMan 5.3 software for Meta-analysis. A total of 10 RCTs were included, with a total of 979 patients. Meta-analysis results showed that in terms of interventricular septal thickness(MD=-0.70, 95%CI[-1.15,-0.24], P=0.003), left ventricular posterior wall thickness(MD=-0.81, 95%CI[-1.41,-0.21], P=0.008), left ventricular mass index(MD=-8.75, 95%CI[-17.40,-0.10], P=0.05), systolic blood pressure(MD=-8.97, 95%CI[-13.46,-4.48], P<0.000 1), diastolic blood pressure(MD=-5.87, 95%CI[-8.39,-3.34], P<0.000 01) and left ventricular end-diastolic diameter(MD=-1.73, 95%CI[-2.38,-1.08], P<0.000 01), Compound Danshen Dripping Pills combined with conventional antihypertensive drugs was superior to conventional antihypertensive drugs. In terms of left ventricular ejection fraction(MD=0.41, 95%CI[-0.74, 1.55], P=0.49), there was no statistical difference in treatment between the two groups. Because of the small amount of literatures included in the safety aspect, it is impossible to give an accurate conclusion. The GRADE score showed that the level of evidence was low and extremely low. The results show that the Compound Danshen Dripping Pills combined with conventional antihypertensive drugs may effectively improve the clinical efficacy for hypertensive ventricular hypertrophy, and the safety needs to be further explored. Due to the low quality of the included literatures, more high-quality RCTs are needed for verification.
Antihypertensive Agents/adverse effects* ; China ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Hypertrophy, Left Ventricular/drug therapy* ; Stroke Volume ; Treatment Outcome ; Ventricular Function, Left

BACKGROUNDAngiotensin converting enzyme (ACE) inhibitors and β-blockers (βB) have beneficial effects on left ventricular (LV) remodeling, alleviate symptoms and reduce morbidity and mortality in patients with chronic heart failure (CHF). However the correlation between the d osages of ACE inhibitors, βB, and recovery of LV structure remains controversial. Clinical factors associated with recovery of normal ventricular structure in CHF patients receiving medical therapy are poorly defined. Here we aimed to identify variables associated with recovery of normal or near-normal structure in patients with CHF.

METHODSWe recruited 231 consecutive CHF outpatients, left ventricular ejection fraction (LVEF) ≤ 40% and left ventricular end diastolic diameter (LVEDD) > 55/50 mm (male/female), who were receiving optimal pharmacotherapy between January 2001 and June 2009, and followed them until December 31, 2009. They were divided into three groups according to LVEDD and whether they were still alive at final follow-up: group A, LVEDD ≤ 60/55 mm (male/female); group B, LVEDD > 60/55 mm (male/female); and group C, those who died before final follow-up. Apart from group C, univariate analysis was performed followed by Logistic multivariate analysis to determine the predictors of recovery of LV structure.

RESULTSA total of 217 patients completed follow-up, and median follow-up time was 35 months (range 6 - 108). Twenty-five patients died during that period; the all-cause mortality rate was 11.5%. Group A showed clinical characteristics as follows: the shortest duration of disease and shortest QRS width, the lowest N-terminal brain natriuretic peptide (NT-proBNP) at baseline, the highest dose of βB usage, the highest systolic blood pressure (SBP), diastolic blood pressure (DBP) and the lowest New York Heart Association (NYHA) classification, serum creatinine, uric acid, total bilirubin and NT-proBNP after treatment. Logistic multivariate analysis was performed according to recovery or no recovery of LV structure. Data showed that LVEF at follow-up (P = 0.013), mitral regurgitation at baseline (P = 0.020), LVEDD at baseline (P = 0.031), and βB dosage (P = 0.041) were independently associated with recovery of LV diameter.

CONCLUSIONOur study suggests that four clinical variables may predict recovery of LV structure to normal or near-normal values with optimal drug therapy alone, and may be used to discriminate between patients who should receive optimal pharmacotherapy and those who require more aggressive therapeutic interventions.

Adrenergic beta-Antagonists ; therapeutic use ; Adult ; Aged ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Female ; Heart Failure ; drug therapy ; physiopathology ; Heart Ventricles ; drug effects ; Humans ; Male ; Middle Aged ; Ventricular Function, Left ; drug effects ; Ventricular Remodeling ; drug effects

OBJECTIVEAlthough several reports documented the association of congenital hypothyroidism (CH) and left ventricular (LV) function in infants or neonates, right ventricular (RV) function in neonates with CH has not been previously studied. The aim of the present study was to assess RV function in neonates with CH before and after thyroxine substitution therapy by quantitative tissue velocity imaging (QTVI) and tissue tracking imaging (TTI).

METHODSFifty-two neonates aged 18-28 days (25 males and 27 females) with CH and 35 healthy neonates aged 18-28 days (16 males and 19 females) were studied by QTVI, TTI as well as conventional pulsed-wave Doppler echocardiography (PWD). The standard apical four-chamber view for long-axis motion of the right ventricle was used for echocardiographic evaluation. Peak systolic displacement (D), peak systolic velocity (Vs), peak early (Ve) and late (Va) diastolic velocity of tricuspid annule were measured, Ve/Va ratio was calculated as well. Transtricuspid flow velocity during early diastole (E) and late diastole (A) were also measured by pulsed-wave Doppler echocardiography. PWD and E/A ratio were calculated too. For each neonate, serum hormone levels of TSH, TT(3), TT(4), FT(3) and FT(4) were measured with a standard chemiluminescent immunoassay. After 1 month of levothyroxine (L-T(4)) substitution therapy in CH neonates, all the echocardiographic evaluations and biochemical tests were re-evaluated. Correlation analysis was also made between serum thyroid hormones levels and right ventricular function.

RESULTSThe indices of right ventricular diastolic function by PWD (E and E/A ratio) in CH group were (45 +/- 10) cm/s and (0.8 +/- 0.3), respectively. Compared with controls, E and E/A ratio in CH neonates were significantly lower (P < 0.001, respectively), while A did not differ between the two groups (P > 0.05). QTVI and TTI showed that right diastolic function (Ve and Ve/Va ratio) as well as right systolic function (Vs and D) in CH group were (3.69 +/- 1.38) cm/s, (0.74 +/- 0.19) cm/s, (4.38 +/- 0.63) cm/s and (0.52 +/- 0.12) cm, respectively. CH neonates had significantly lower Ve, Ve/Va ratio, Vs and D of tricuspid annular velocity (P < 0.001, respectively), whereas there was no significant difference in Va between the two groups (P > 0.05). After 1 month of substitutive therapy, CH neonates showed a significant increase of Ve, Ve/Va ratio, Vs, D, E, and E/A ratio, (6.92 +/- 1.86) cm/s, (1.13 +/- 0.22), (5.92 +/- 1.03) cm/s, (0.78 +/- 0.17) cm, (61 +/- 10) cm/s and (1.1 +/- 0.4), respectively (P < 0.001). Those parameters were positively correlated with serum TT(3), TT(4), FT(3) and FT(4) levels (P < 0.01, respectively), and were negatively correlated with serum TSH levels (P < 0.01, respectively).

CONCLUSIONSOur findings suggest that neonates with CH are associated with right ventricular subclinical systolic and diastolic dysfunction, which can be reversed by early L-T(4) substitution therapy. QTVI and TTI are valuable methods to evaluate right ventricular function in neonates. Systolic and diastolic velocities of the tricuspid annulus measured by QTVI and TTI are useful and accurate to assess RV function in neonates.

Adult ; Blood Flow Velocity ; Child, Preschool ; Congenital Hypothyroidism ; physiopathology ; Diastole ; drug effects ; physiology ; Echocardiography ; Echocardiography, Doppler, Pulsed ; Female ; Heart Ventricles ; drug effects ; physiopathology ; Humans ; Male ; Systole ; drug effects ; physiology ; Thyrotropin ; pharmacology ; Thyroxine ; blood ; pharmacology ; Tricuspid Valve ; physiopathology ; Ventricular Function, Left ; drug effects ; physiology ; radiation effects ; Ventricular Function, Right ; drug effects ; physiology

Adrenergic beta-Antagonists ; pharmacology ; Animals ; Cardiopulmonary Resuscitation ; Diastole ; drug effects ; Female ; Male ; Natriuretic Peptide, Brain ; blood ; Propanolamines ; pharmacology ; Rabbits ; Ventricular Function, Left ; drug effects

AIMTo investigate the effect of hypothalamic thyrotropin-releasing hormone (TRH) on cardiac function and its mechanism.

METHODSThe Sprague-Dawley rats were mounted in a stereotaxic apparatus and a guide cannula placed in the left hypophysiotropic area, through which TRH were microinjected in presence or absence of L-NAME and atropine. The left ventricular systolic pressure (LVSP), heart rate (HR) and the maximum velocity of ascending or descending in intraventricular pressure (+/- dp/dt(max)) were recorded.

RESULTS(1) TRH microinjected into the hypophysiotropic area induced a significant increase of LVSP, HR, dp/dt and-dp/dt(max) (P < 0.05, P < 0.01). (2) L-NAME significant increased LVSP and pretreatment with L-NAME inhibited the positive effects induced by TRH. (3) Atropine increased LVSP and dp/dt(max) (P < 0.05), but it significantly descended heart rate (P < 0.05). Pretreatment with atropine weakened the tachycardiac response induced by TRH.

CONCLUSION(1) Hypothalamic TRH can produce positive inotropic and chronotropic response to myocardium. (2) Hypothalamic endogenous NO can descend LVSP, but has no effects on HR, dp/dt(max), and-dp/dt(max). The effect of TRH is through nitric oxide-dependent pathway. (3) Hypothalamic endogenous cholinergic transmitter can produce negative chronotropic and positive inotropic response to myocardium. Hypothalamic TRH mediates cardiac function maybe partly through cholinergic M receptor.

Animals ; Blood Pressure ; Heart Rate ; Heart Ventricles ; drug effects ; Hypothalamus ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Thyrotropin-Releasing Hormone ; administration & dosage ; pharmacology ; Ventricular Function, Left ; drug effects

OBJECTIVETo study the effect of hypertonic saline solution on the left ventricular functions of isolated hearts from burned rats.

METHODSThirty-six Wistar rats were used and divided into 4 groups: (1) normal hearts perfused with isotonic Krebs-Henseleit solution; (2) normal hearts perfused with Krebs-Henseleit solution which contained 215 mmol/L Na+; (3) hearts of rats suffered from 25% TBSA third degree burn and perfused with isotonic Krebs-Henseleit solution; (4) hearts of the burned rats perfused with Krebs-Henseleit solution which contained 215 mmol/L Na+. The systolic and diastolic functions of the left ventricle were observed.

RESULTSDuring perfusion, there were very short periods of decrease in heart systolic and diastolic functions at first, but they recovered very soon and even became stronger than normal both in the normal and burned rats. The systolic and diastolic functions of the hearts increased very significantly when the perfusion solution was changed to isotonic solution from the hypertonic solutions. The effect of the hypertonic saline solution on the ventricular systolic and diastolic improvements was stronger in the hearts of the burned rats than that in the normal hearts.

CONCLUSIONSHypertonic saline solution can directly affect myocardium and significantly improve the ventricular systolic and diastolic functions, especially in the hearts of the burned rats.

Animals ; Burns ; physiopathology ; Female ; Heart ; drug effects ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Saline Solution, Hypertonic ; pharmacology ; Ventricular Function, Left ; drug effects

OBJECTIVETo investigate the relationship between the U wave on electrocardiogram and the midmyocardium in rabbit left ventricle free wall in vivo.

METHODSThe monophasic action potentials in the epicardium, midmyocardium, and endocardium of the left ventricle free wall were recorded simultaneously in 16 rabbits. The rabbits were then given an intravenous injection of Sotalol (1, 1.5 and 2.0 mg/kg) in 30 minutes intervals, and measurements were taken.

RESULTSIn the basic condition, there were no U wave on electrocardiogram. The U wave appeared after the intravenous Sotalol at 1.5 mg/kg, and the U wave became greater with increased dosage of intravenous Sotalol (2 mg/kg). The repolarization duration of the midmyocardium was prolonged longer than that of the epicardium and endocardium by Sotalol, and the repolarization duration of the epicardium coincided with the apex of the T wave, The repolarization duration of the midmyocardium coincided with the end point of the U wave.

CONCLUSIONThe U wave may originate from the delayed repolarization of the midmyocardium.

Action Potentials ; drug effects ; Animals ; Anti-Arrhythmia Agents ; pharmacology ; Dose-Response Relationship, Drug ; Electrocardiography ; Endocardium ; drug effects ; physiology ; Heart Ventricles ; drug effects ; Pericardium ; drug effects ; physiology ; Rabbits ; Sotalol ; pharmacology ; Ventricular Function

The purpose of the present study was to investigate the effect of meperidine on rat ventricular muscle. Cardiac function was assessed in Langendorff-perfused rat hearts and intracellular calcium level was recorded in enzymatically isolated rat ventricular myocytes using spectrofluorometric techniques. To explore the underlying mechanism, whole-cell configuration of patch-clamp technique was used to record L-type Ca(2+) current. The results showed that meperidine decreased the product of heart rate and left ventricular developed pressure (LVDP HR), maximal rate of the left ventricular pressure increase (LV +dP/dt(max)) and decrease (LV -dP/dt(max)), but increased left ventricular end-diastolic pressure in a dose-dependent manner (0-1000 micromol/L). Meperidine also produced a dose-dependent reduction in electrically induced [Ca(2+)](i) transient amplitude and an increase in diastolic [Ca(2+)](i) baseline level, but did not alter the caffeine (20 mmol/L) induced Ca(2+) release from intracellular ryanodine-sensitive Ca(2+) stores. Meperidine at 100 micromol/L inhibited L-type Ca(2+) current to 67.4 10.1% of control but did not affect the voltage dependency of activation and inactivation. The inhibitory effect of meperidine on Ca(2+) current could not be prevented by pretreatment with the opioid receptor antagonist naloxone. These data suggest that meperidine exerts a negative inotropic effect by inhibiting L-type Ca(2+) current. The lack of effect of naloxone implies that the action is independent of the opioid receptor.
Animals ; Calcium Channels, L-Type ; drug effects ; Depression, Chemical ; Dose-Response Relationship, Drug ; Heart Rate ; drug effects ; Male ; Meperidine ; pharmacology ; Myocardial Contraction ; drug effects ; Myocytes, Cardiac ; metabolism ; Patch-Clamp Techniques ; Rats ; Rats, Sprague-Dawley ; Ventricular Function, Left ; drug effects