Evaluation of cardiac contractility of fetuses from pregestational diabetes mellitus pregnancies by three-dimensional ultrasound

SUMMARY OBJECTIVE: This study aimed to evaluate cardiac contractility in fetuses from pregestational diabetes mellitus pregnancies by three-dimensional ultrasound using spatiotemporal image correlation in rendering mode. METHODS: A retrospective cross-sectional study was performed on 40 fetuses from nondiabetic pregnancies and 28 pregestational diabetic pregnancies between 20 and 33 weeks and 6 days. Cardiac contractility was assessed by measuring the ventricular myocardial area in diastole subtracted from the ventricular myocardial area in systole. RESULTS: Pregestational diabetic pregnancies had a lower maternal age than nondiabetic pregnancies (26.7 vs. 39.9 years, p=0.019). Cardiac contractility in fetuses from diabetic and nondiabetic pregnancies was similar (p=0.293). A moderately positive and significant correlation was observed between gestational age and cardiac contractility (r=0.46, p=0.0004). A 1-week increase in gestational age was responsible for a 0.1386 cm2 increase in cardiac contractility. CONCLUSION: Cardiac contractility as evaluated by three-dimensional ultrasound using spatiotemporal image correlation in rendering mode showed no significant differences across fetuses with and without pregestational diabetes.

Canagliflozin reduces the contractile response of isolated heart of normal adult rats / Canagliflozin reduce la respuesta contráctil del corazón aislado de ratas adultas normales

SUMMARY: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent a unique class of glucose-declining renal-targeted drugs. The SGLT2i Canagliflozin (CANA) is an anti-hyperglycemic drug that reduces various cardiovascular and renal outcomes in patients with type 2 diabetes mellitus. This study aimed to explore the potential effects of CANA on the isolated healthy adult rat hearts to show if CANA has positive inotropic or cardiac depressant effects via analyzing the amplitude and frequency of cardiac contractions. In isolated normal adult rat hearts, the effects of CANA on cardiac contractility were examined. In a dose-response curve, CANA led to a significant cardiac depressant effect in a dose-dependent manner. This cardiac depressant effect of CANA (10-6 M) was not prevented by atropine. However, this cardiac depressant effect was partially antagonized by both Isoproterenol (10-5 M) and Calcium chloride (10-6 M), suggesting beta-adrenoceptor and calcium channel blocking actions. In addition, the cardiac depressant effect of CANA (10-6 M) was mitigated in part by Nitric oxide synthase inhibitor, L-NAME, suggesting that its action probably depends to some extent on the accumulation of nitric oxide, which decreases the rise of intracellular Calcium. Data from this study demonstrate that CANA has a significant cardiac relaxant effect in isolated hearts of healthy adult rats by different possible mechanisms. This inhibitory effect on cardiac contractility may help improve the diastolic ventricular filling providing a therapeutic potential to help the other cardioprotective mechanisms of CANA in the prevention and treatment of heart failure.

RESUMEN: Los inhibidores del cotransportador de sodio- glucosa 2 (SGLT2i) representan una clase única de fármacos dirigidos a los riñones que disminuyen la glucosa. El SGLT2i Canagliflozin (CANA) es un fármaco antihiperglucémico que reduce varios resultados cardiovasculares y renales en pacientes con diabetes mellitus tipo 2. Este estudio tuvo como objetivo explorar los efectos potenciales de CANA en corazones aislados de ratas adultas sanas para indicar si CANA tiene efectos inotrópicos o depresores cardíacos positivos mediante el análisis de la amplitud y la frecuencia de las contracciones cardíacas. En corazones aislados de ratas adultas normales, se examinaron los efectos de CANA sobre la contractilidad cardíaca. En una curva de dosis-respuesta, CANA condujo a un efecto depresor cardíaco significativo de manera dependiente de la dosis. Este efecto depresor cardíaco de CANA (10-6 M) no fue impedido por la atropina. Sin embargo, este efecto depresor cardíaco fue parcialmente antagonizado tanto por el isoproterenol (10-5 M) como por el cloruro de calcio (10-6 M), lo que sugiere acciones bloqueadoras de los receptores beta adrenérgicos y de los canales de calcio. Además, el efecto depresor cardíaco de CANA (10-6 M) fue mitigado en parte por el inhibidor de la sintasa de óxido nítrico, L-NAME, lo que sugiere que su acción probablemente depende en cierta medida de la acumulación de óxido nítrico, lo que disminuye el aumento de calcio intracelular. Los datos de este estudio demuestran que CANA tiene un efecto relajante cardíaco significativo en corazones aislados de ratas adultas sanas por diferentes mecanismos posibles. Este efecto inhibitorio sobre la contractilidad cardíaca puede ayudar a mejorar el llenado ventricular diastólico proporcionando un potencial terapéutico para ayudar a los otros mecanismos cardioprotectores de CANA en la prevención y tratamiento de la insuficiencia cardíaca.

Fresh and Decayed Stem Juice of Musa acuminata x balbisiana (Musa paradisiaca) Reduce the Force and Rate of Contractility of an Isolated Perfused Rabbit Heart.

Background: Decaying stem juice of Musa acuminata × balbisiana is commonly used by local communities and traditional herbalist in Central Uganda in the management of cardiovascular conditions like hypertension. Aims: The study investigated the ionotropic and chronotropic effect of fresh and decaying stem juice of Musa acuminata × balbisiana on the isolated perfused rabbit heart. Materials and Methods: Methods. Study Design: An experimental study. Place and Duration of Study: Study was done at the Dept of Pharmacology & Therapeutics Pharmacology Lab between December 2012 to March 2013. Experimental Procedure: An experimental study determined the effects of fresh and decayed stem juices of Musa acuminate X balbisiana on the rate and force of contraction of an isolated rabbit heart using Langendorff’s heart perfusion experiment and methods. The heart rate (beats/minute) was determined. The force of contraction of the heart was determined by measuring the height of each peak on the kymogram. Results: The force and rate of contractility of an isolated perfused rabbit decreased with increasing doses of the stem juice from 0.156 mg/mL to 100mg/mL for both the fresh and decayed stem juice of M. acuminata. The decrease could be associated with the high [K+] ions that decrease the membrane potential or cause hyperpolarization the myocardial cell membranes leading to reduced force and rate of heart contractility. The effect of the fresh stem juice was short lived and at very high concentrations, it caused a cardiac arrest while the effect of the decayed stem juice was prolonged. Conclusion: Fresh and decayed stem juice of Musa acuminata × balbisiana have compounds that cause a negative ionotropic and chronotropic effect on an isolated perfused rabbit heart.

Interaction between Bupivacaine, Ropivacaine and Diltiazem in the Isolated Rat Heart / 대한마취과학회지

BACKGROUND: Local anesthetics are often used for a regional block in patients who are being treated with calcium channel blockers (CCB). Bupivacaine is a local anesthetic with potential for serious cardiovascular toxicity. Ropivacaine is a relatively new local anesthetic. It is clinically equipotent and chemically similar to bupivacaine. Diltiazem (CCB) is a potent coronary and systemic vasodilator with antiarrhythmic properties. Local anesthetics such as bupivacaine and ropivacaine have been suggested to show drug interactions with diltiazem. Therefore, we tried to observe the drug interactions between bupivacaine, ropivacaine and diltiazem using an animal model. METHODS: This study was performed using an isolated rat heart (N = 40) by the Langendorff method. After a stabilization period, all hearts were subjected to the application of local anesthetics of a 1 microgram/ml or 3/ml concentration, respectively. Thereafter, they were subdivided into four groups; the bupivacaine (B) group, bupivacaine with diltiazem (BD) group, ropivacaine (R) group, and ropivacaine with diltiazem (RD) group. Parameters such as, LVP, dp/dt, heart rate (HR), coronary flow (CF), DO2, and MVO2 were measured. RESULTS: All parameters decreased in all groups, respectively (P < 0.05). The BD group and R group showed a lower LVP and dp/dt than those of the B group (P < 0.05). The BD group and B group showed lower HR than that of the R group (P < 0.05). The RD group showed a higher CF than other groups (P < 0.05). CONCLUSIONS: The negative inotropic potency of bupivacaine was enhanced in the presence of diltiazem. We suggest that diltiazem has a protective effect against reduction of CF by ropivacaine. Therefore, we should consider this when selecting local anesthetics for cardiovascular patients under the treatment of diltiazem.

A Comparison of the Effects of Isoflurane and Desflurane on Myocardial Contractility in Isolated Sprague-Dawley Hearts / 대한마취과학회지

BACKGROUND: Desflurane has some cardiovascular effects similar to isofl-urane. Desflurane has decreased systemic vascular resistance and demonstrated a myocardial depressant property in vivo animal stulies. The purpose of this study was to compare the myocardial and coronary effects of desflurane and isoflurane. METHODS: Cardiac effects were examinated in 24 rat hearts perfused with modified Krebs solution containing 1 MAC and 2 MAC desflurane or isoflurane for 10 min. at each concentration in a retrograde manner. Left ventricle pressure, heart rate and rate of change of ventricular pressure (dp/dt) were mea-sured, as were coronary flow and partial oxygen pressure. Oxygen delivery, myocardial oxygen consumption and percent oxygen extraction were calculated by each measurement. RESULTS: Heart rate, left ventricle pressure and dp/dt decreased each anesthetic similarly in a concentration-dependent manner. Heart rate decreased by 243.86 15.7 beats/min at 1 MAC and 219.14 15.8 beats/min at 2 MAC with isoflurane (control: 262.99 2.35 beats/min.) and by 250 23 beats/min at 1 MAC and 223.89 23 beats/min at 2MAC with desflurane (control 266.94 22.30 beats/min). Coronary flow increased by 13.72 0.99 ml/g/min at 1 MAC and 14.30 1.05 ml/g/min at 2 MAC with isoflurane (control :12.04 0.84 ml/g/min) and by 12.80 1.63 ml/g/min at 1 MAC and 13.71 1.46 ml/g/min at 2 MAC with desflurane (control 14.04 1.22 ml/g/min). Oxygen delivery increased proportionally with coronary flow. The increase in MVO2 was accompanied by a decrease in heart rate and pressure but there were no significant differences. Percent oxygen extraction decreased in a concentration dependent manner. CONCLUSIONS: This study shows that desflurane and isoflurane decreased heart rate, myocardial depression and coronary vasodilating effects, resulting in improved oxygen perfusion effects.

Effects of Enflurane on the Left Ventricular Function in Isolated Diltiazem-Pretreated Rat Heart / 대한마취과학회지

BACKGROUND: Calcium channel blockers and volatile anesthetics have depressant effects on cardiac function. Both of them appear to exert, qualitatively and quantitatively, different effects on myocardial contractility, coronary flow, and myocardial oxygen balance. The aim of this study was to examine the direct cardiac effects of the enflurane in the presence of diltiazem. METHODS: Isolated Sprague-Dawley rat hearts (N=45) were perfused at constant pressure with oxygenated Modified-Krebs solution (pH 7.4, 37oC). Isovolumetric left ventricular pressure (LVP) and dP/dt were measured via a latex balloon and transducer. Also, coronary flow and oxygen tensions at the coronary inflow and outflow were measured. After stabilization period, all hearts were subjected to the application with diltiazem (100 ng/ml). Thereafter, they were subdivided into three groups; group 1, 2, 3. Groups subjected to the combination of diltiazem (100 ng/ml) with enflurane 1.1, 2.2, or 3.3 vol%, respectively. RESULTS: After the application of diltiazem, myocardial contractility and heart rate were significantly decreased, and coronary flow were significantly increased. The combination of diltiazem with enflurane depressed myocardial contractility, heart rate, myocardial O2 consumption, and percentage of O2 extraction more than diltiazem alone, and their effects were dependent on the concentration of enflurane. However, there was no difference in the change of coronary flow and oxygen delivery between diltiazem and the combination of diltiazem with enflurane. CONCLUSIONS: These in vitro findings demonstrate that the combination of diltiazem with enflurane shows greater direct negative inotropic and negative chronotropic effect, and is associated with less attenuation of coronary autoregulation, but with a larger reduction in O2 utilization. The present results suggest that high enflurane anesthesia in the diltiazem-pretreated patients could result in profound cardiac depression.

The Effect of Desflurane on Myocardial Contractility and Coronary Flow in Isolated Rat Hearts / 대한마취과학회지

Background: Desflurane, a fluorinated methyl-ethyl ether, has some advantageous properties including low blood solubility, stability in soda lime, and resistance to biodegradation. Desflurane in vivo has demonstrated myocardial depressant property. The purpose of this study was to test the direct effects of desflurane on myocardial contractile function and coronary flow in the isolated heart. Methods: Twelve isolated rat hearts were continuously perfused with modified Krebs solution containing 6, 9 and 12 vol% of desflurane for 10 min at each concentration. Systolic left ventricular pressure and rate of change of ventricular pressure (dp/dt) were measured. Heart rate and coronary flow were also measured. To differentiate direct vasodilatory effect of desflurane from an indirect metabolic effect due to autoregulation of coronary flow, oxygen delivery, myocardial oxygen consumption and percent oxygen extraction were calculated. Results: Heart rate (control 266+/-22 beats/min) decreased to 250+/-23 beats/min at 6 vol%, 236+/-26 beats/min at 9 vol% and 223+/-22 beats/min at 12 vol% of desflurane. Systolic left ventricular pressure and dp/dt decreased in a concentration-dependent manner. In spite of decrement of myocardial oxygen consumption, coronary flow (control 12.0+/-1.2 ml/min) increased to 12.8+/-1.6 ml/min at 6 vol%, 12.9+/-1.6 ml/min at 9 vol% and 13.7+/-1.4 ml/min at 12 vol% of desflurane. Oxygen delivery increased proportionally with coronary flow. Percent oxygen extraction decreased in a concentration-dependent manner. Conclusion: These results suggest that desflurane has a direct myocardial depressing and coronary vasodilating effect in a concentration-dependent manner.