oxytocin and Myocardial-Ischemia

Ischemic heart disease (IHD) is among the most important and top ranked causes of death in the world, and its preventive and interventional mechanisms are actively being investigated. Preconditioning may still be beneficial in some situations such as IHD. Development of cardioprotective agents to improve myocardial function, to decrease the incidence of arrhythmias, to delay the onset of necrosis, and to limit the total extent of infarction during IHD is of great clinical importance. In order to reduce morbidity, a new treatment modality must be developed, and oxytocin may indeed be one of the candidates. There is increasing experimental evidence indicating that oxytocin may have cardioprotective effects either by decreasing the extent of reperfusion injury or by pharmacologic preconditioning activity. This review shows that in the presence of oxytocin, the cardioprotective effects may be increased to some extent. The presented board of evidence focuses on the valuable effects of oxytocin on myocardial function and candidates it for future clinical studies in the realm of ischemic heart diseases.

Topics: Arrhythmias, Cardiac; Cardiotonic Agents; Coronary Artery Disease; Humans; Ischemic Preconditioning, Myocardial; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Necrosis; Oxytocin

We have demonstrated that entire oxytocin (OT) system is synthesized in the rat and human heart and this hormone is implicated in several cardiac functions including stem cells differentiation into cardiomyocytes. These observations led us to the invention of OT as an inducer of cardiomyogenesis (US20060205636A1). We also proposed the use of OT, its functional derivatives, and/or physiological precursors as well as nucleic acids capable of encoding OT as cell-differentiating and useful agents for treating or preventing diseases, such as heart diseases associated with loss of cardiomyocytes. The invention is relevant to the use of OT or OT-related compounds. OT is claimed as an inducer that promotes the differentiation of non-cardiomyocytes (e.g. stem/progenitor cells) in situ, which can be used to repair, restore or fortify damaged cardiac tissue or in cell culture in order to provide material for cell or tissue grafting in the heart. Recent reports documented the significant progress in the research on the role of OT in cardiovascular regulation. Most of the results are consistent with the postulated cardioprotective role of OT. In this review, new data are discussed in the context of the main points presented in the invention.

Topics: Animals; Cardiac Surgical Procedures; Cardiotonic Agents; Cell Differentiation; Disease Models, Animal; Humans; Models, Cardiovascular; Muscle Development; Myocardial Ischemia; Myocytes, Cardiac; Oxytocin; Regeneration; Signal Transduction; Stem Cell Transplantation; Stem Cells

ECG changes, similar to those seen during myocardial ischaemia, together with symptoms of chest pain, are common during Caesarean section (CS). We hypothesized that oxytocin administration has cardiovascular effects leading to these symptoms and ECG changes.. Forty women undergoing elective CS under spinal anaesthesia were given an i.v. bolus of either 10 IU of oxytocin (Group OXY-CS, n=20) or 0.2 mg of methylergometrine (Group MET-CS, n=20), in a double-blind, randomized fashion after delivery. Ten healthy, non-pregnant, non-anaesthetized women were used as normal controls (Group OXY-NC, n=10) and were given 10 IU of oxytocin i.v. Twelve-lead ECG, on-line, computerized vectorcardiography (VCG), and invasive arterial pressure were recorded.. Oxytocin produced a significant increase in heart rate, +28 (SD 4) and +52 (3) beats min(-1) [mean (SEM); P<0.001], decreases in mean arterial pressure, -33 (2) and -30 (3) mm Hg (P<0.001), and increases in the spatial ST-change vector magnitude (STC-VM), +77 (12) and +114 (8) microV (P<0.001), in CS patients and controls, respectively. Symptoms of chest pain and subjective discomfort were simultaneously present. Methylergometrine produced mild hypertension and no significant ECG changes.. Oxytocin administered as an i.v. bolus of 10 IU induces chest pain, transient profound tachycardia, hypotension, and concomitant signs of myocardial ischaemia according to marked ECG and STC-VM changes. The effects are related to oxytocin administration and not to pregnancy, surgical procedure, delivery, or sympathetic block from spinal anaesthesia.

Topics: Adult; Anesthesia, Obstetrical; Anesthesia, Spinal; Blood Pressure; Cesarean Section; Double-Blind Method; Electrocardiography; Female; Heart Rate; Humans; Intraoperative Care; Intraoperative Complications; Methylergonovine; Myocardial Ischemia; Oxytocics; Oxytocin; Pregnancy

What is the central question of this study? Could the activation of oxytocin or oestrogen receptors be protective against myocardial injury after ovariectomy? If so, would exercising have an additional ameliorating effect? What is the main finding and its importance? The results revealed that when accompanied by exercise, both oestrogen receptor agonists and oxytocin improved cardiac dysfunction, inhibited the generation of pro-inflammatory cytokines and reduced myocardial injury in ovariectomized female rats, suggesting a new approach for protecting postmenopausal women against ischaemia-induced myocardial injury. To investigate the putative protective effects of oxytocin or oestrogen receptor agonists against myocardial injury of ovariectomized sedentary or exercised rats, female Sprague-Dawley rats assigned to sham-operated control and ovariectomized (OVX) groups were kept sedentary or undertook swimming exercise for 4 weeks and were treated with saline, an oestrogen receptor (ER) β (DPN) or ERα agonist (PPT) or oxytocin. Ovariectomy increased weight gain and anxiety in sedentary rats, whereas exercise prevented weight gain. When accompanied by exercise, both ER agonists and oxytocin inhibited weight gain and anxiety; oxytocin, in the absence or presence of exercise, increased the left ventricular diastolic dimensions and ejection fraction, whereas ER agonists also increased left ventricular diameter when given to exercised rats. Upon the induction of myocardial ischaemia-reperfusion in the OVX rats, plasma creatine kinase-(muscle-brain) was depressed by PPT and oxytocin, whereas DPN, PPT and OT reduced plasminogen activator inhibitor-1 concentrations. The increased tumour necrosis factor-α concentration in OVX rats was also suppressed by exercise or DPN, PPT or oxytocin treatments, whereas the interleukin-6 concentration was diminished by all the treatments when given in conjunction with exercise. Disorganization of cardiac muscle fibres was reduced in all exercised rats. Oestrogen receptor agonists, as well as oxytocin, in conjunction with exercise may be effective new therapeutics to protect against myocardial ischaemia in postmenopausal women.

Topics: Animals; Creatine Kinase; Estrogen Receptor alpha; Estrogens; Female; Interleukin-6; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocytes, Cardiac; Ovariectomy; Oxytocin; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Tumor Necrosis Factor-alpha

A 38-year-old pregnant woman underwent cesarean section with combined spinal epidural anesthesia. Immediately after intravenous administration of oxytocin, she developed chest and bilateral shoulder pain. Simultaneously, face flushing and ST segment depression on electrocardiogram were observed. Her blood pressure decreased and heart rate increased. She was treated with bolus injection of phenylephrine and continuous infusion of nicorandil and noradrenaline. At the end of surgery, all the symptoms disappeared. Because oxytocin may induce myocardial ischemia probably due to coronary vasoconstriction and peripheral vasodilation, it is important for anesthesiologists to note that oxytocin should be given to patients as slowly as possible. Alternative agents such as mythylergometrine may be used safely for an individual who is susceptive to oxytocin.

Topics: Adult; Cesarean Section; Female; Humans; Myocardial Ischemia; Oxytocics; Oxytocin; Pregnancy

Ischemia-reperfusion injury is a common complication of heart disease that is the leading cause of death worldwide. Here, we plan to elucidate oxytocin cardioprotection effects against ischemia-reperfusion via nitric oxide (NO), reactive oxygen species (ROS), and protein kinase C (PKC) in anesthetized rat preconditioned myocardium. Forty-eight Sprague-Dawley rats were equally divided into eight groups. All animals were subjected to 25 min ischemia and 120 min reperfusion. Oxytocin (OT), L-NAME (LNA, a nitric oxide synthase inhibitor), chelerythrine (CHE, a PKC enzyme inhibitor), and N-acetylcysteine (NAC, a ROS scavenger) were used prior to ischemia. Results showed that mean arterial pressure significantly reduced during the first 10 min of ischemia and reperfusion in IR, LNA, CHE, and NAC groups (p<0.05). OT prevented mean arterial pressure decline during early phase of ischemia and reperfusion. Cardioprotective effects of OT in infarct size, plasma levels of creatine kinase-MB and lactate dehydrogenase, severity and incidence of ventricular arrhythmias were abolished by L-NAME, chelerythrine, and N-acetylcysteine (p<0.05). The present study showed that OT pretreatment reduces myocardial infarct size and ventricular arrhythmias, and improves mean arterial pressure via NO production, PKC activation, and ROS balance. These findings provide new insight into therapeutic strategies for ischemic heart disease.

Topics: Animals; Male; Myocardial Ischemia; Nitric Oxide; Oxytocin; Protein Kinase C; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

Maternal heart disease during pregnancy is the main cause of obstetric morbidity and mortality. We report the case of a 40-year-old woman with a history of myocardial infarction and percutaneous transluminal coronary angioplasty. The patient suffered a second heart attack and received pharmacologic treatment. After admission, she was seen to be 29 weeks pregnant. Delivery was by cesarean section under progressive epidural block without complications. We review the medical, obstetric, and anesthetic implications of myocardial infarction during pregnancy. The management of such patients should be multidisciplinary and decisions about delivery should be taken based on obstetric considerations.

Topics: Adult; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cesarean Section; Combined Modality Therapy; Contraindications; Coronary Angiography; Diagnosis, Differential; Elective Surgical Procedures; Ergotamine; Female; Humans; Myocardial Infarction; Myocardial Ischemia; Obesity, Morbid; Oxytocin; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy, High-Risk; Recurrence; Stents; Thrombophilia

Topics: Adult; Cesarean Section; Female; Humans; Intraoperative Complications; Myocardial Ischemia; Oxytocin; Pregnancy

Topics: Adult; Cesarean Section; Female; Humans; Myocardial Ischemia; Oxytocin; Postoperative Complications; Pregnancy

Synthetic oxytocin (Syntocinon) can be shown to reduce or abolish ST-T changes induced experimentally by hypoxaemia alone, by hypoxaemia and ergometrine, by vasopressin, and by a new procedure involving injection of small doses of picrotoxin into the lateral cerebral ventricle. Ventricular fibrillation induced by picrotoxin can also be reversed by oxytocin. These effects suggest a probable metabolic action of oxytocin against cardiac anoxic changes, and its possible therapeutic usefulness as an antagonist of myocardial ischaemia. It is speculated that this might be a physiological action of the hormone.

Topics: Animals; Arginine Vasopressin; Electrocardiography; Ergonovine; Hypoxia; Myocardial Ischemia; Oxytocics; Oxytocin; Rabbits; Vasopressins