endothelin-1 and Shock--Cardiogenic

The seriousness of scorpion envenomation results essentially from left cardiac function with pulmonary oedema and/or a state of shock. Adrenergic myocarditis, toxic myocarditis and myocardial ischemia are the 3 mechanisms that explain the cardiac dysfunction. Myocardial ischemia is not only due to the release of catecolamines but also the effect of the cytokines and/or neuropeptide Y on the coronary vessels. The cardiac damage can be due or enhanced by the depressive effect of the cytokines on the myocardial cells. The frequently observed hyperglycaemia only enhances the state of the already damaged myocardium.

Topics: Acidosis; Animals; beta-Thromboglobulin; Blood Platelets; Catecholamines; Cytokines; Endothelin-1; Humans; Hyperglycemia; Myocardial Ischemia; Myocarditis; Myocardium; Neuropeptide Y; Pulmonary Edema; Scorpion Stings; Scorpion Venoms; Scorpions; Shock, Cardiogenic; Stress, Physiological

In ST segment elevation acute myocardial infarction (STEMI), the endothelin (ET) system imbalance, reflected by the circulating ET-1:ET-3 ratio has not been investigated. This study's primary objective was to measure the circulating ET-1:ET-3 ratio and correlate it with the risk stratification for 1 year mortality of STEMI based on TIMI score. On admission, the TIMI risk score and at discharge, the dynamic TIMI risk score were calculated in 68 consecutive subjects with STEMI. Subjects with high TIMI risk score were associated with higher mean ET-1 level and ET-1:ET-3 ratio. The ET-1:ET-3 ratio more accurately predicted the high on admission TIMI risk score than the ET-1 level. Subjects with high dynamic TIMI risk score were associated with higher mean ET-1 level and ET-1:ET-3 ratio. The ET-1:ET-3 ratio more accurately predicted the high at discharge dynamic TIMI risk score than ET-1 level. From multivariable analysis, the ET-1:ET-3 ratio was not independently associated with high on admission TIMI risk score but independently predicted high at discharge dynamic TIMI risk score (odds ratio = 9.186,

Topics: Adult; Aged; Cardiotonic Agents; Electric Countershock; Electrocardiography; Endothelin-1; Endothelin-3; Female; Heart Failure; Hospital Mortality; Humans; Male; Middle Aged; Patient Admission; Patient Discharge; Percutaneous Coronary Intervention; Prognosis; Prospective Studies; Recurrence; Risk Assessment; Risk Factors; Shock, Cardiogenic; ST Elevation Myocardial Infarction; Treatment Outcome; Ventricular Fibrillation

We investigated the short-term effects of a phosphodiesterase III inhibitor (Olprinone) on hemodynamics and thoracic duct lymph flow in anesthetized open-chest sheep with heart failure induced by endothelin-1 (cardiogenic shock). Ultrasound transit-time flow probes were attached to the thoracic duct, the ascending aorta and the renal artery. Arterial, pulmonary and central venous pressures were monitored. Endothelin-1 was infused intravenously at a dosage that reduced cardiac output to 50% or more of baseline (n=11). The effects of Olprinone were examined (n=5) by intravenous infusion after endothelin-1 administration. Other sheep (n=6) were used as controls. Olprinone significantly increased cardiac output that had been decreased by endothelin-1 and further increased thoracic duct flow that had been increased by endothelin-1. Increased arterial and pulmonary pressures induced by endothelin-1 administration were rapidly decreased by Olprinone. Renal arterial flow and central venous pressure were, however, unchanged by Olprinone. Overall, Olprinone acutely improved experimental cardiogenic shock (heart failure) induced by endothelin-1, and maintained thoracic duct lymph flow at a high level after endothelin-1 administration.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Cardiac Output; Central Venous Pressure; Cyclic Nucleotide Phosphodiesterases, Type 3; Disease Models, Animal; Endothelin-1; Enzyme Inhibitors; Female; Heart Failure; Imidazoles; Lung; Male; Models, Cardiovascular; Pyridones; Renal Circulation; Sheep; Shock, Cardiogenic; Thoracic Duct; Time Factors; Treatment Outcome; Vascular Resistance

Recently, several types of centrifugal pumps have been widely used as the main pumps for cardiopulmonary bypass (CPB). However, according to the results of our experimental studies, after cardiogenic shock, pulsatile flow was effective in maintaining the functions and microcirculations of end organs, especially those of the liver and kidney. To estimate the effectiveness of pulsatility during CPB, cytokine and endothelin and other metabolic parameters were measured in clinical pulsatile and nonpulsatile CPB cases. From March to May 1997, CPB was performed in 18 elective cases (14 ischemic and 4 valvular disease). In 9 cases, pulsatile perfusion was achieved by the Jostra HL20, which is a newly developed CPB pump (Group P). A nonpulsatile centrifugal pump was used in 9 patients (Group NP). In both groups, as chemical and metabolic mediators, interleukin-8 (IL-8), endothelin-1 (ET-1), and plasma free hemoglobin were measured before and during CPB, and 0.5, 3, 6, 9, 18 h after weaning from CPB. This pulsatile CPB pump could be very simply and easily controlled and could easily produce pulsatile flow. There were no significant differences in CPB time (CPBT), aortic cross clamp time (ACCT), mean aortic pressure, or pump flow during CPB between the both groups. The ET-1 level of Group P was significantly (p < 0.05) lower than that of Group NP 9 h after CPB weaning. The IL-8 level of Group P also showed a lower value than that of Group NP. As for plasma free hemoglobin, there were no significant differences between the groups. These results suggested that even in conventional CPB, pulsatility was effective to reduce endothelial damage and suppress cytokine activation. It may play a important role in maintaining the functions and microcirculations of end organs during CPB.

Topics: Aged; Aorta; Blood Pressure; Cardiopulmonary Bypass; Coronary Artery Bypass; Elective Surgical Procedures; Endothelin-1; Endothelium, Vascular; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Hemoglobins; Humans; Interleukin-8; Kidney; Liver; Male; Microcirculation; Middle Aged; Myocardial Ischemia; Pulsatile Flow; Shock, Cardiogenic; Time Factors

This study was designed to test the hypothesis that the properties of novel 1,4-dihydropyridine PCA50941 could favor the recovery of cardiogenic shock. Coronary blood flow (CBF), measured with an electromagnetic flow probe placed on the left circumflex coronary artery, systemic arterial pressure and heart rate were recorded in 24 anesthetized goats; left ventricular pressure and dP/dt were also recorded in 19 of these goats. Under control conditions, intracoronary injections in 5 goats of PCA50941 (10-120 microg) caused smaller reductions of CBF than those of Bay K 8644 (0.3-10 microg) (the reduction of CBF by 120 microg PCA50941 was 25% and that by 10 microg Bay K 8644 was 43%), and i.v. infusions in 4 goats of PCA50941 (10-300 microg/min) did not modify CBF nor the other hemodynamic variables recorded, whereas i.v infusion of Bay K 8644 (10-30 microg/min) reduced CBF by 20% and increased arterial pressure, left ventricular pressure and dP/dt. During control conditions and endothelin-induced cardiogenic shock, respectively, the values for 15 goats were: for CBF, 33+/-4 vs. 16+/-4 ml/min; for mean arterial pressure, 88+/-4 vs. 60+/-5 mm Hg; for left ventricular systolic pressure, 102+/-5 vs. 75+/-4 mm Hg; for dP/dt, 1453+/-147 vs. 925+/-101 mm Hg/s (all P<0.05), and for heart rate, 77+/-6 vs. 81+/-6 beats/min (P>0.05). Intravenous infusion of PCA50941 (100 microg/min) reversed the hemodynamic variables from the shock state to control values within 20 min in 5 of 6 animals, whereas i.v. administration of Bay K 8644 (10-30 microg/min) was not effective in 4 of 5 animals, and the vehicle (DMSO) was not effective in none of 4 animals in reversing the hemodynamic shock state. Therefore, it is suggested that PCA50941, a novel 1,4-dihydropyridine, has a cardiovascular profile that might be suitable for treating cardiogenic shock states.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Animals; Blood Flow Velocity; Blood Pressure; Calcium Channel Agonists; Coronary Circulation; Dihydropyridines; Endothelin-1; Female; Goats; Heart; Heart Rate; Infusions, Intravenous; Shock, Cardiogenic; Thiazoles; Ventricular Function, Left