piperidines and Cardiovascular-Abnormalities

Role of 2-Deoxy-D-glucose (2-DG) in reversing the Indian red scorpion (Mesobuthus tamulus concanesis Pocock, MBT) venom-induced toxicity was examined. Femoral arterial pressure, ECG and respiratory movements were recorded in urethane anesthetized rats. Plasma glucose and serum insulin levels were also estimated. Intravenous injection of 5 mg/kg MBT venom produced immediate decrease in mean arterial pressure, heart rate and respiratory frequency followed by an increase and subsequent progressive decrease. ECG pattern exhibited ischaemic changes. There was hyperinsulinemia after venom without corresponding decrease in plasma glucose. The animals died within 37 +/- 9 min and demonstrated significant increase in pulmonary water content. 2-DG pretreatment (0.5 g/kg, iv) improved the cardiopulmonary abnormalities induced by venom and the animals survived for nearly 120 min. There was no hyperinsulinemia and increased pulmonary water content in these animals. In insulin (2 IU/kg) treated rats, the MBT venom-induced cardiopulmonary abnormalities were attenuated and ECG abnormalities were reversed. The pulmonary water content in these animals exhibited a decreasing trend and the animals survived for 120 min. Repaglinide (10 microg/kg, iv) pretreatment failed to reverse the venom-induced cardiopulmonary changes including the increased pulmonary water content. The survival time was similar to venom only group. The present results reveal that 2-DG reverses the venom-induced cardiopulmonary toxicity probably by restoring insulin sensitivity.

Topics: Anesthesia; Animals; Blood Glucose; Carbamates; Cardiovascular Abnormalities; Deoxyglucose; Hyperglycemia; India; Insulin; Lung Diseases; Myocardial Ischemia; Piperidines; Pulmonary Edema; Rats; Respiration; Scorpion Venoms; Ultrasonography

Ligating the right lateral vitelline vein of chicken embryos (venous clip) results in cardiovascular malformations. These abnormalities are similar to malformations observed in knockout mice studies of components of the endothelin-1 (ET-1)/endothelin-converting enzyme-1/endothelin-A receptor pathway. In previous studies we demonstrated that cardiac ET-1 expression is decreased 3 h after clipping, and ventricular diastolic filling is disturbed after 2 days. Therefore, we hypothesise that ET-1-related processes are involved in the development of functional and morphological cardiovascular defects after venous clip.. In this study, ET-1 and endothelin receptor antagonists (BQ-123, BQ-788 and PD145065) were infused into the HH18 embryonic circulation. Immediate haemodynamic effects on the embryonic heart and extra-embryonic vitelline veins were examined by Doppler and micro-particle image velocimetry. Ventricular diastolic filling characteristics were studied at HH24, followed by cardiovascular morphologic investigation (HH35).. ET-1 and its receptor antagonists induced haemodynamic effects at HH18. At HH24, a reduced diastolic ventricular passive filling component was demonstrated, which was compensated by an increased active filling component. Thinner ventricular myocardium was shown in 42% of experimental embryos.. We conclude that cardiovascular malformations after venous clipping arise from a combination of haemodynamic changes and altered gene expression patterns and levels, including those of the endothelin pathway.

Topics: Animals; Aspartic Acid Endopeptidases; Blood Flow Velocity; Cardiac Output; Cardiovascular Abnormalities; Cells, Cultured; Chick Embryo; Echocardiography; Endothelin Receptor Antagonists; Endothelin-1; Endothelin-Converting Enzymes; Gene Expression Regulation, Developmental; Heart; Heart Rate; Hemodynamics; Laser-Doppler Flowmetry; Ligation; Metalloendopeptidases; Myocardium; Oligopeptides; Peptides, Cyclic; Piperidines; Receptors, Endothelin; RNA, Messenger; Signal Transduction; Time Factors; Veins; Ventricular Function; Yolk Sac